AU2008200694A1 - Method of treating acromegaly, hyperprolactinemia, portal hypertension and gastrointestinal bleeding with somatostatin-dopamine chimeric analogs - Google Patents

Description

GRIFFITH HACK PATENTS, TRADE MARKS, IP LAW

SPECIFICATION

OF

PATENT APPLICATION

COUNTRY

TYPE

TITLE

AUSTRALIA

Patent METHOD OF TREATING ACROMEGALY, HYPERPROLACTINEMIA, PORTAL HYPERTENSION AND GASTROINTESTINAL BLEEDING WITH SOMA TOSTATIN- DOPAMINE CHIMERIC ANALOGS SOCIETE DE CONSEILS DE RECHERCHES ET D'APPLICATIONS SCIENTIFIQUES, S.A.S.

APPLICANT

AUSTRALIA

Patents Act 1990 COMPLETE SPECIFICATION Standard Patent Applicant(s): SOCIETE DE CONSEILS DE RECHERCHES ET D'APPLICATIONS SCIENTIFIQUES, S.A.S.

Invention Title: METHOD OF TREATING ACROMEGALY, HYPERPROLACTINEMIA, PORTAL HYPERTENSION AND GASTROINTESTINAL BLEEDING WITH SOMATOSTATIN- DOPAMINE CHIMERIC ANALOGS The following statement is a full description of this invention, including the best method for performing it known to me/us:

I

00 1

O

0 METHOD OF TREATING ACROMEGALY, HYPERPPROLACTINEMIA, PORTAL HYPERTENSION AND C GASTROINTESTINAL BLEEDING WITH SSOMATOSTATIN-DOPAMI NE CHIMERIC ANALOGS Background of the Invention

O

[001] The present invention is drawn to somatostatin-dopamine chimeric analogs C and methods relating to their therapeutic use.

00 0 [002] Dopamine is a catecholamine neurotransmitter that has been implicated in the

O

CN 10 pathogenesis of both Parkinson disease and schizophrenia. Dopamine and related molecules have been shown to inhibit the growth of several types of malignant tumors in mice, and this activity has been variously attributed to inhibition of tumor-cell proliferation, stimulation of tumor immunity or as well as effects on melanin metabolism in malignant melanomas. Recent studies demonstrated the presence of D2 dopamine receptors on endothelial cells. Dopamine has recently been reported to strongly and selectively inhibit at non-toxic levels the vascular permeabilizing and angiogenic activities of VPF/VEGF.

1003] Somatostatin a tetradecapeptide has been shown to have potent inhibitory effects on various secretory processes in tissues such as pituitary, pancreas and gastrointestinal tract. SS also acts as a neuromodulator in the central nervous system. These biological effects of SS, all inhibitory in nature, are elicited through a series of G protein coupled receptors, of which five different subtypes have been characterized (SSTR-1 SSTR-5). These five subtypes have similar affinities for endogenous SS ligands, but have differing distributions in various tissues. Somatostatin binds to the five distinct receptor (SSTR) subtypes with relatively high and equal affinity for each subtype.

[004] There is evidence that SS regulates cell proliferation by arresting cell growth via SSTR-1, and -5 subtypes, and/or by inducing apoptosis via SSTR-3 subtype. SS and various analogues have been shown to inhibit normal and neoplastic cell proliferation in vitro and in vivo via specific SS receptors (SSTR's) and possibly different postreceptor actions. In addition, there is evidence that distinct SSTR subtypes are expressed in normal and neoplastic human tissues, conferring different tissue H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 7/02/08 00- 2-

O

0 affinities for various SS analogues and variable clinical response to their therapeutic effects.

S[005] Binding to different types of somatostatin receptor subtypes is associated with the treatment of various conditions and/or diseases. For example, the inhibition of growth hormone has been attributed to the somatostatin type-2 receptor ("SSTR-2"), while the inhibition of insulin has been attributed to the somatostatin type-5 receptor \0 Activation of types 2 and 5 have been associated with growth hormone Ssuppression and more particularly growth hormone secreting adenomas (acromegaly) 00 and thyroid stimulating hormone (TSH) secreting adenomas. Activation of type 5 but O 10 not type 2 receptor has been associated with treating prolactin secreting adenomas.

Other indications associated with activation of the somatostatin receptor subtypes include inhibition of insulin and/or glucagon for treating diabetes mellitus, angiopathy, proliferative retinopathy, dawn phenomenon, and nephropathy; inhibition of gastric acid secretion for treating peptic ulcers, enterocutaneous and pancreaticocutaneous fistula, irritable bowel syndrome, Dumping syndrome, watery diarrhea syndrome, AIDS related diarrhea, chemotherapy-induced diarrhea, acute or chronic pancreatitis and gastrointestinal hormone secreting tumors; treatment of cancer such as hepatoma; inhibition of angiogenesis; treatment of inflammatory disorders such as arthritis; retinopathy; chronic allograft rejection; angioplasty; preventing graft vessel and gastrointestinal bleeding. Preferably, a somatostatin analog is selective for the specific somatostatin receptor subtype or subtypes responsible for the desired biological response to reducing interaction with other receptor subtypes which could lead to undesirable side effects or loss of efficacy.

[006] Somatostatin and its receptors (SSTR-1 to SSTR-5) are expressed in normal human parafollicular C cells and medullary thyroid carcinoma (MTC). MTC is a tumor originating from thyroid parafollicular C cells that produces calcitonin (CT), somatostatin, and several other peptides. It was recently demonstrated that SS and SSTR's are expressed in human MTC, and SS and SS analogues were shown to induce a decrease in plasma CT levels and provide symptomatic improvement in MTC patients.

Another recent study has shown that SS and SS analogs, in particular, SSTR-1 and SSTR-2, can inhibit the proliferation of tumor cells, suggesting that specific SSTR subtypes can function in MTC cell growth regulation. The development and H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 7/02/08 3- 00 0 characterization of SSTR subtype analogues that selectively effect MTC cell growth is useful for clinical and therapeutic applications.

Summary of the Invention 1007] The present invention is based on our discovery of somatostatin-dopamine j chimeric analogs, comprising compounds that retain both somatostatin and dopamine \0 activity. The chimeric analogs of the invention are considered to be useful, in Svitro, for use as research tools, diagnostic assays, etc., or in vivo, for use as diagnostic or 00 therapeutic agents. Preferred chimeric analogs of the invention display enhanced activity when compared to native somatostatin and dopamine, either alone or in combination.

[008] Accordingly, in a first aspect, the invention features a chimeric analog comprising at least one moiety which binds to one or more somatostatin receptor(s) and at least one moiety which binds to one or more dopamine receptor(s), or a pharmaceutically acceptable salt thereof.

1009] In a first embodiment of the first aspect, the chimeric analog comprises formula Y- (L)m--Z (W)n

'N-

R1 R3 H R2"" x

N

R4

(I)

wherein: [0010] X is H, Cl, Br, I, F, -CN, Cl-o alkyl, Clo 1 0 heteroalkyl, C 2 10 alkenyl, C 2 10 alkynyl, substituted C- 0 lo alkyl, substituted Cl- 1 0 heteroalkyl, substituted C 2 1 0 alkenyl, or substituted C2- 1 0 alkynyl; [0011] RI is H, Cl-lo alkyl, Cl- 0 o heteroalkyl, C2- 1 0 alkenyl, C 2 10 alkynyl, substituted C-o 1 0 alkyl, substituted C.-o 0 heteroalkyl, substituted C2- 10 alkenyl, substituted C2- 1 0 alkynyl, or -CN; H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 7/02/08 00 4 0 [0012] R2 and R3, each is, independently, H or absent, provided that when R2 and R3 are absent a double bond is present between the carbon atoms to which they are Sattached; [0013] R4 is H, C 1 -o 1 alkyl, C-1lo heteroalkyl, C2-1 0 alkenyl, C 2 10 alkynyl, substituted C-o 1 0 alkyl, substituted Cl-io heteroalkyl, substituted C2- 10 alkenyl, or substituted C2- 10 Salkynyl; S[00141 Y is -S-(CH 2 -S(0) 2 or 00 [0015] L is -(CH 2 when Y is -S(0) 2 or or L is O 10 C(0)-(CR7R8)q-C(0)-, when Y is or or L is (amino acid)t, when Y is

-S-(CH

2 or 10016] W is -CR9,R10-; [0017] R5 and R6 each is, independently, H, C.-lo alkyl, substituted Cl-io alkyl; Cl-lo heteroalkyl, substituted Ci.o 1 heteroalkyl, C2-1 0 alkenyl, substituted C2- 1 0 alkenyl, C2- 1 0 alkynyl, substituted C2-1 0 alkynyl, aryl, alkylaryl, or substituted alkylaryl; 10018] R7, R8, R9, and RIO each is, independently, H, F, Cl, Br, I, C.o 1 0 alkyl, substituted CI.lo alkyl; C-.lo heteroalkyl, substituted Ci-lo heteroalkyl, C2- 1 0 alkenyl, substituted C2- 1 0 alkenyl, C 2 10 alkynyl, substituted C2- 1 0 alkynyl, aryl, alkylaryl, or substituted akylaryl; or R7 and R8 can, optionally, join together to form a ring system; or R9 and R10 can, optionally, join together to form a ring system; [0019] i is 1-10, provided that when i is 1, then R1 is not H, C1-4 alkyl, allyl, alkenyl or -CN, R4 is not H or -CH 3 R5, R6, R7 and R8 each is, independently, not H or C-.s alkyl, L is not X is not H, Cl, Br, I, F, -CN, or C-.s alkyl, or R9 and RIO each is, independently, not H; 10020] m is 0 or 1; [0021] n is 0-10; [0022] pis 1-10; 10023] q is [0024] sis 1-10; 10025] t is 1-10; [0026] Z is a ligand of at least one somatostatin receptor; 10027] or a pharmaceutically acceptable salt thereof; and H;\araR\Keep\peci\P64463-div-SPECI.doC 7/02/08 00- 5 00 O [0028] wherein each moiety depicted between the brackets is, independently for each Soccurrence, attached to an N-terminal or an internal amine group, carboxylic acid group Sor hydroxyl group of Z.

[0029] In a second aspect of the first embodiment, the chimeric analog comprises formula (II), 100301 H 0

HN

o N 0 -R1 R3 H

N

R4

(II)

wherein: [0030] X is H, Cl, Br, I, F, -CN, Cl-lo alkyl, Cl-.o heteroalkyl, C2- 10 alkenyl, C2-1 0 alkynyl, substituted C-o 1 0 alkyl, substituted C.-lo heteroalkyl, substituted C2- 1 0 alkenyl, or substituted C 2 1 0 alkynyl; (00311 RI is H, Ci-lo alkyl, Ci-lo heteroalkyl, C2- 1 0 alkenyl, C2- 1 0 alkynyl, substituted Ci-o 1 alkyl, substituted Ci-o 1 heteroalkyl, substituted C2-1 0 alkenyl, substituted C 2 1 0 alkynyl, or -CN; [00321 R2 and R3, each is, independently, H or absent, provided that when R2 and R3 are absent a double bond is present between the carbon atoms to which they are attached; [00331 R4 is H, C.-lo alkyl, CI-lo heteroalkyl, C2-1 0 alkenyl, C2- 1 0 alkynyl, substituted Cl-lo alkyl, substituted Cl-lo heteroalkyl, substituted C 2 1 0 alkenyl, or substituted C2- 1 0 alkynyl; [0034] R5 is H, Cl-.o alkyl, C.

0 lo heteroalkyl, C 2 1 0 alkenyl, C2- 10 alkynyl, substituted Cl-lo alkyl, substituted Ci-lo heteroalkyl, substituted C2- 1 0 alkenyl, substituted C2- 1 0 alkynyl, or a group of the formula of-(CH 2 )rN(R 1,R12); H:OtaraR\Keep\Speci\P64463-div-SPECI.doc 7/02/08 -6- 00 [00351 Y is or -N(R8)- 100361 L is -(CH 2 when Y is or or L is -C(O)-(CR9R1O)qwhen Y is or or L is (amino acid)t, when Y is SC(0)-, -N(R8)-(CH 2 or [00371 W is -CR9,R 100381 R6, R7, and R8 each is, independently, H, CI- 1 0 alkyl, substituted CI- 10 alkyl,

C

1 10 heteroalkyl, substituted CI- 1 0 heteroalkyl, C 2 10 alkenyl, substituted C 2 1 0 aikenyl, 00 C 2 10 alkynyl, substituted C 2 1 0 alkynyl, aryl, aikylaryl, or substituted akylaryl; 100391 R9 and RIO each is, independently, H, Cl, Br, I, F, CI- 10 alkyl, substituted Cl.

1o alkyl; C 1 10 heteroalkyl, substituted CI- 10 heteroalkyl, C 2 10 alkenyl, substituted C 2 10 alkenyl, C 2 10 alkynyl, substituted C 2 1 0 alkynyl, aryl, alkylaryl, or substituted akylaryl; or R9 and RiO0 can, optionally, join together to form a ring system; [00401 RI 1 and R12 each is, independently, H, CI- 10 alkyl, substituted C 1 10 alkyl;

C

1 10 heteroalkyl, substituted C 1 1 0 heteroalkyl, C 2 10 alkenyl, substituted C 2 10 alkenyl,

C

2 10 alkynyl, substituted C 2 10 alkynyl, aryl, alkylaryl, or substituted akylaryl; 100411 i is 1 -10, provided that when i is 1, then RI is not H, C 14 alkyl, allyl, alkenyl or -CN, R4 is not H or -CH 3 R5 is not C 1 5 alkyl group or a group of the formula of

(CH

2 )rN(CH 3 R6, R7, R8, R9 and RIO0 each is, independently, not H or C 1 5 alkyl, L is not or X is not H, Cl, Br, 1, F, -CN, or C 1 5 alkyl; 100421 m is 0 or 1; 100431 n is 2-10; 100441 p is 1-10; [00451 q is [00461 r is 1-8; [00471 s is 1-10; [00481 t isi1-10; [00491 v is 2-3; [0050] Z is a ligand of at least one somatostatin receptor; or [00511 a pharmaceutically acceptable salt thereof;, and H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 7/02/08 7- 00 7 0 [0052] wherein each moiety depicted between the brackets is, independently for each Soccurrence, attached to an N-terminal or an internal amine group, carboxylic acid group Sor hydroxyl group of Z.

[0053] In a third embodiment of the first aspect, t he chimeric analog of claim 1, wherein said chimeric analog comprises formula (III), R1 R4- R1 00 R2

(III)

wherein: 10054] R2 is H, -N(R11)N(R12,R13), -N(R6R7), or -COOH; [0055] R4 and R5 each is, independently, H, Cl- 1 o alkyl, substituted Ci.o 1 alkyl; Ci.lo heteroalkyl, substituted Ci-lo heteroalkyl, C2- 1 0 alkenyl, substituted C2-10 alkenyl, C2- 10 alkynyl, substituted C2- 10 alkynyl, aryl, alkylaryl, substituted akylaryl or R8-C(O)-; 100561 W is -CR9R10- or -(CH 2 )q-NH-(CH 2 100571 R1, R6, R7, R8, R11, R12 and R13 each is, independently, H, C.

1 0 o alkyl, substituted Ci.lo alkyl; Cl.-o heteroalkyl, substituted C 1 -1o heteroalkyl, C2- 10 alkenyl, substituted C2- 1 0 alkenyl, C2- 10 alkynyl, substituted C2-1 0 alkynyl, aryl, alkylaryl, or substituted akylaryl; 10058] R9 and R10 each is, independently, H, -OH, -CN, -NO 2 C, Br, I, C- 1 0 alkyl, substituted Ci-lo alkyl; C.- 1 o heteroalkyl, substituted Cl-io heteroalkyl, C2- 1 0 alkenyl, substituted C 2 1 0 alkenyl, C2- 10 alkynyl, substituted C2- 1 0 alkynyl, akylaryl, substituted alkylaryl, or aryl; 100591 X is C.o 1 0 alkyl, substituted CI-lo alkyl; Ci-lo heteroalkyl, substituted C-.lo heteroalkyl, C2- 10 alkenyl, substituted C2- 1 0 alkenyl, C2- 1 0 alkynyl, substituted C2- 1 0 alkynyl, akylaryl, substituted alkylaryl, aryl, or acyl; [0060] Q is C or N; provided that when Q is N, then R2 is absent; [0061] i is 1-10; 100621 n is 1-6; 10063] q is 1-6; [0064] r is 1-8; H:\MaraR\Keep\Speci\P64463-div-SPECI.doC 7/02/08 00 8-

O

[0065] Z is a ligand of at least one somatostatin receptor; or [0066] a pharmaceutically acceptable salt thereof; and [0067] wherein each moiety depicted between the brackets is, independently for each occurrence, attached to an N-terminal or an internal amine group or hydroxyl group of

Z.

[0068] In a fourth embodiment of the first aspect, the chimeric analog comprises O formula (IV), 00 R2.

N-0 z (W)n R3 R1

(IV)

wherein: [0069] R1 and R2 each is, independently, H, Ci.lo alkyl, substituted Cl-lo alkyl; Cl-io heteroalkyl, substituted Ci-lo heteroalkyl, C2- 10 alkenyl, substituted C2-1 0 alkenyl, C2- 10 alkynyl, substituted C2-1 0 alkynyl, aryl, alkylaryl, or substituted akylaryl; [00701 R3, R4, R5, R6 and R7 each is, independently, H, -OH, -CN, -NO 2 F, Cl, Br, I, Cl-lo alkyl, substituted Cl-io alkyl; Cl-lo heteroalkyl, substituted Cl-lo heteroalkyl, C 2 to alkenyl, substituted C2- 1 0 alkenyl, C2- 10 alkynyl, substituted C2- 10 alkynyl, aryl, alkylaryl, or substituted akylaryl; [0071] W is [00721 Y is or acyl; [0073] m is 0-10; [0074] n is 1-6; 10075] Z is a ligand of at least one somatostatin receptor; or [0076] a pharmaceutically acceptable salt thereof; and [0077] wherein each moiety depicted between the brackets is, independently for each occurrence, attached to an N-terminal or an internal amine group or hydroxyl group of

Z.

H:\araR\Keep\Speci\P64463-di-SPECI.doC 7/02/08 00 9 0 S[00781 In a fifth embodiment of the first aspect, the chimeric analog comprises formula S R2 P< NW)<

Y--Z

P

N

X R1 \0 (V) Swherein:

(N

00 [0079] P is -N(R3R4) or H; 010 10080] X is N or S; [0081] W is -CR5R6-; 10082] Y is -(CR7R8)m-C(O)-; [0083] RI, R3 and R4 each is, independently, H, Cio 1 0 alkyl, substituted Cl-lo alkyl; Ci-lo heteroalkyl, substituted Ci-io heteroalkyl, C2-10 alkenyl, substituted C2- 1 0 alkenyl,

C

2 -1 0 alkynyl, substituted C2- 1 0 alkynyl, aryl, alkylaryl, or substituted akylaryl; 10084] R2, R5, R6, R7 and R8 each is, independently, H, -OH, -CN, -NO 2 F, Cl, Br, I, Cl.io alkyl, substituted Ci-io alkyl; Ci.o 1 heteroalkyl, substituted Ci.lo heteroalkyl, C2o1 alkenyl, substituted C2- 1 0 alkenyl, C2- 1 0 alkynyl, substituted C2- 10 alkynyl, aryl, alkylaryl, or substituted akylaryl; [0085] i is 1-10; [0086] m is 0-10; [0087] n is 0-6; [0088] Z is a ligand of at least one somatostatin receptor; or [0089] a pharmaceutically acceptable salt thereof; and [0090] wherein each moiety depicted between the brackets is, independently for each occurrence, attached to an N-terminal or an internal amine group or hydroxyl group of

Z.

[0091] In a sixth aspect of the first embodiment, the chimeric analog comprises formula (VI), FR1. .Y--Z H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 7/02/08 10 00

(VI)

wherein: [0092] Y is -(CR2R3)m,-C(O)- or acyl; 10093] RI is H, C 1 .lo alkyl, substituted Cl-.o alkyl; Cl.o 10 heteroalkyl, substituted Cl-o 1 0 heteroalkyl, C 2 10 alkenyl, substituted C2- 10 alkenyl, C 2 10 alkynyl, substituted C 2 10 alkynyl, aryl, alkylaryl, or substituted akylaryl; S100941 R2 and R3 each is, independently, H, -OH, -CN, -NO 2 F, Cl, Br, I, Cl-o 10 00 alkyl, substituted Cl.o 10 alkyl; Cl-o 10 heteroalkyl, substituted CI.

10 o heteroalkyl, C 2 10 alkenyl, substituted C 2 10 alkenyl, C 2 10 alkynyl, substituted C2-.

10 alkynyl, aryl, alkylaryl, or substituted akylaryl; 100951 i is 1-10; 100961 m is 0-10; 100971 Z is a ligand of at least one somatostatin receptor; or [0098] a pharmaceutically acceptable salt thereof; and 10099] wherein each moiety depicted between the brackets is, independently for each occurrence, attached to an N-terminal or an internal amine group or hydroxyl group of

Z.

[0100] In a seventh embodiment of the first aspect, the chimeric analog comprises formula (VII), R1

N

PN-Y-L--Z

S R2

(VII)

wherein: 101011 P is -N(R3R4) or H; [01021 L is -(CR5R6)m-C(O)- or acyl; [0103] Y is Cl-lo alkyl, substituted C 1 1 lo alkyl; Cl.

1 lo heteroalkyl, substituted Ci.- 1 lo heteroalkyl, C 2 10 alkenyl, substituted C 2 10 alkenyl, C2- 10 alkynyl, substituted C2- 1 0 alkynyl, aryl, alkylaryl, substituted akylaryl, or absent; 101041 RI, R2, R5 and R6 each is, independently, H, -OH, -CN, -NO 2 F, Cl, Br, I, Cl-o 1 0 alkyl, substituted C.

10 o alkyl; Cl-o 1 0 heteroalkyl, substituted Cl-o 1 0 heteroalkyl, C 2 10 H:\MaraR\Keep\SpeCi\P64463-div-SPECI.doc 7/02/08 00- 11-

O

0 alkenyl, substituted C 2 1 0 alkenyl, C2- 10 alkynyl, substituted C2-1 0 alkynyl, aryl, alkylaryl, or substituted akylaryl; 101051 R3 and R4 each is, independently, H, C-o 1 0 alkyl, substituted Cl-lo alkyl; Ci-lo heteroalkyl, substituted Cl-lo heteroalkyl, C2- 10 alkenyl, substituted C2- 1 0 alkenyl, C2- 10 alkynyl, substituted C2-1 0 alkynyl, aryl, alkylaryl, or substituted akylaryl; [0106] i is 1-10; \0 [0107] m is 0-10; [0108] Z is a ligand of at least one somatostatin receptor; or 00 [0109] a pharmaceutically acceptable salt thereof; and [0110] wherein each moiety depicted between the brackets is, independently for each occurrence, attached to an N-terminal or an internal amine group or hydroxyl group of

Z.

[0111] In an eighth embodiment of the first aspect, the chimeric analog comprises formula (VIII), R2 R3 R4

N

S R 1 Z

(VIII)

wherein: [0112] X and Y each is, independently, -OH, -OR4 or [0113] L is -(CR3R4)m-C(O)- or acyl; [0114] R1, R2, R3 and R4 each is, independently, H, -OH, F, Cl, Br, I, -CN, NO 2 Cl-lo alkyl, substituted Ci-lo alkyl; Ci.lo heteroalkyl, substituted C.o 1 0 heteroalkyl, C2- 10 alkenyl, substituted C2- 1 0 alkenyl, C2-1 0 alkynyl, substituted C2- 1 0 alkynyl, aryl, alkylaryl, or substituted akylaryl; or R2 and R3 can, optionally, join together to form a ring system; [01151 R5 is H, C-.lo alkyl, substituted Cio 1 0 alkyl; Ci-lo heteroalkyl, substituted C 1 -io heteroalkyl, C2- 10 alkenyl, substituted C2- 10 alkenyl, C 2 1 0 alkynyl, substituted C2- 1 0 alkynyl, aryl, alkylaryl, or substituted akylaryl; [01161 i is 1-10; :\MaraR\Keep\Speci\P64463-div-SPECI.doc 7/02/08 00 12 00 0 [0117] mis 0-10; [0118] Z is a ligand of at least one somatostatin receptor; or 1[0119] a pharmaceutically acceptable salt thereof; and wherein each moiety depicted between the brackets is, independently for each occurrence, attached to an N-terminal or an internal amine group or hydroxyl group of

Z.

0 [0120] In a ninth embodiment of the first aspect, the chimeric analog comprises Sformula (IX), 00 R3

N.

z ^y R2 Y R1

(IX)

wherein: [0121] X and Y each is, independently, -OH, -OR4 or R7-C(O)-; [0122] Q is -(CR5R6)m-C(O)- or acyl; [0123] R1, R2, R3, R4, R5 and R6 each is, independently, H, -OH, F, Cl, Br, I, -CN,

NO

2

CI-

10 alkyl, substituted C-o 10 alkyl; C 1 .io heteroalkyl, substituted C.lo 0 heteroalkyl,

C

2 10 alkenyl, substituted C2- 10 alkenyl, C2- 1 0 alkynyl, substituted C2-1 0 alkynyl, aryl, alkylaryl, or substituted akylaryl; or R1 and R2 can, optionally, join together to form a ring system; or R3 and R4 can, optionally, join together to form a ring system; [0124] R7 is H, Cl.

1 0 alkyl, substituted Ci-o 1 alkyl; C 1 .io heteroalkyl, substituted Ci.lo heteroalkyl, C 2 10 alkenyl, substituted C2- 1 0 alkenyl, C 2 1 0 alkynyl, substituted C2- 1 0 alkynyl, aryl, alkylaryl, or substituted akylaryl; [0125] i is 1-10; 10126] m is 0-10; [0127] Z is a ligand of at least one somatostatin receptor; or [0128] a pharmaceutically acceptable salt thereof; and H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 7/02/08 00- 13 0 [0129] wherein each moiety depicted between the brackets is, independently for each Soccurrence, attached to an N-terminal or an internal amine group or hydroxyl group of C Z.

101301 In a tenth embodiment of the first aspect, the chimeric analog comprises formula

N

O R6 R3 R7 00 R2 R1 R4 L i

(X)

wherein: [01311 Y is -(CR8R9)m-C(O)- or acyl; 10132] R1, R2, R3, R4, R5, R6, R7, R8 and R9 each is, independently, H, -OH, F, Cl, Br, I, -CN, NO 2

C-

1 0 alkyl, substituted Cl- 10 alkyl; Ci-lo heteroalkyl, substituted Ciheteroalkyl, C2- 1 0 alkenyl, substituted C2- 1 0 alkenyl, C2- 1 0 alkynyl, substituted C2- 1 0 alkynyl, aryl, alkylaryl, or substituted akylaryl; [01331 i is 1-10; [01341 m is 0-10; [0135] Z is a ligand of at least one somatostatin receptor; or [0136] a pharmaceutically acceptable salt thereof; and [0137] wherein each moiety depicted between the brackets is, independently for each occurrence, attached to an N-terminal or an internal amine group or hydroxyl group of

Z.

[0138] In another embodiment of the first aspect, the chimeric analog comprises any of the compounds listed in Table 1; or a pharmaceutically acceptable salt thereof.

[0139] In another embodiment of the first aspect, the chimeric analog comprises a compound according to the formula of: Dop2-DPhe-Doc-DPhe-cyclo[Cys-3ITyr-DTrp-Lys-Val-Cys]-Thr-NH2, Dop2-DPhe-Doc-DPhe-cyclo[Cys-3 ITyr(Dop2)-DTrp-Lys-Val-Cys]-Thr-NH 2 Ac-Lys(Dop2)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Ac-DLys(Dop2)-DPhe-cyclo[Cys-3ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 H:\araR\Keep\Speci\P64463-div-SPEC.dOC 7/02/08 00 14 Dop3 -DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop4-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 -DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 00 Dop5-Lys(Dop5)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DPhe-cyclo[Cys-3 ITyr(Dop2)-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 or Dop2-DLys(Dop2)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 or a pharmaceutically acceptable salt thereof.

101401 In a preferred embodiment of the first aspect, the chimeric analog comprises a compound according to the formula of- Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH2, Dop2-DLys(Dop2)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 or Dop2-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 or a pharmaceutically acceptable salt thereof.

[0141] In a more preferred embodiment of the first aspect, the chimeric analog comprises a compound according to the formula of Dop2-Lys(Dop2)-DTyr-DTyrcyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2; or a pharmaceutically acceptable salt thereof. In another more preferred embodiment, the chimeric analog comprises a compound according to the formula of Dop2-DLys(Dop2)-cyclo [Cys-Tyr- DTrp- Lys- Abu-Cys]-Thr-NH2; or a pharmaceutically acceptable salt thereof. In yet another more preferred embodiment, the chimeric analog comprises a compound zccording to the H:\MaraR\Keep\Specl\P64463-div-SPECI .doc 7/02/08 00- 15 0 O formula of Dop2-DPhe-cyclo[Cys-3ITyr-DTrp-Lys-Thr-Cys]-Thr-NH2; or a pharmaceutically acceptable salt thereof.

[0142] In another embodiment of the first aspect, the chimeric analog comprises a compound according to the formula of: Dop2-Lys(Dop2)-DTyr-Tyr-cyclo[DDab-Arg-Phe-Phe-DTrp-Lys-Thr-Phe], Dop2-Tyr-cyclo[DDab-Arg-Phe-Phe-DTrp-Lys-Thr-Phe], or \0 Dop2-DTyr-DTyr-Caeg-cyclo[DCys-3Pal-DTrp-Lys-Dcys]-Thr(Bzl)-Tyr-NH 2 Sor 00 a pharmaceutically acceptable salt thereof [0143] In a second aspect, the invention features a compound useful as an intermediate in a chemical synthesis, wherein said intermediate comprises a compound according to formula or (27) (referred to herein as intermediate compound and respectively) as shown below:

O

N

H OH 0 -s

N

6 OH

O

H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 7/02/08 16 00

X

0

-OH

or H:\MaraR\Keep\Speci\P64461-div-SPECI .doc 7/02/08 17 00 0" 0 t N

OH

H

27 or an organic or inorganic salt thereof.

101441 In a third aspect, the invention features a method of eliciting a dopamine receptor agonist effect in a subject in need thereof, wherein said method comprises administering to said subject an effective amount of a chimeric analog of the invention, 00 wherein said chimeric analogue comprises a compound according to the formula of C] Formula (111), (VI) (VII), (VIII), or or a pharmaceutically acceptable salt thereof;, or intermnediate compound or or an organic or inorganic salt thereof; and wherein said effective amount is the amount effective to elicit a dopamine receptor agonist effect in said subject.

101451 In a first embodiment of the third aspect, the chimeric analog comprises any of the compounds listed in Table 1; or a pharmaceutically acceptable salt thereof.

101461 In a second embodiment of the third aspect, the chimeric analog comprises a compound according to the formnula of: Dop2-DPhe-Doc-DPhe-cyclo[Cys-3lTyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop2-DPhe-Doc-DPhe-cyclo [Cys-3 ITyr(Dop2)-DTrp-Lys-Val-Cys]-Thr-NH 2 Ac-Lys(Dop2)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Ac-DLys(Dop2)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop3 -DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, Dop2-DLys(Dop2)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 H:\M.araR\Keep\Speci\P64463-div-SPECI .doc 7/02/08 00 18 Dop2-DPhe-cyclo [Cys-3 ITyr(Dop2)-DTrp-Lys-VaI-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 or Dop2-DLys(Dop2)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 or a pharmaceutically acceptable salt thereof.

00 10147] In a preferred embodiment, the chimeric analog comprises a compound according to the formnula of:.

Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH2, Dop2-DLys(Dop2)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 or Dop2-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-CysI-Thr-NH 2 or a pharmnaceutically acceptable salt thereof.

101481 In a more preferred embodiment of the third aspect, the chimeric analog comprises a compound according to the formula of Dop2-Lys(Dop2)-DTyr-DTyrcyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2; or a pharmaceutically acceptable salt thereof.

[01491 In another more preferred embodiment of the third aspect, chimeric analogue comprises a compound according to the formula of Dop2-DLys(Dop2)-cyclo[Cys-Tyr- DTrp-Lys-Abu-Cys]-Thr-NH2; or a pharmaceutically acceptable salt thereof. In yet another more preferred embodiment of the third aspect, chimeric analogue comprises a compound according to the formula of Dop2-DPhe-cyclo[Cys-3ITyr-DTrp-Lys-Thr- Cys]-Thr-NH2; or a pharmaceutically acceptable salt thereof.In a third embodiment of the third aspect, the chimeric analogue comprises a compound according to the formula of: Dop2-Lys(Dop2)-DTyr-Tyr-cyclo [DDab-Arg-Phe-Phe-DTrp-Lys-Thr-Phe], Dop2-Tyr-cyclo [DDab-Arg-Phe-Phe-DTrp-Lys-Thr-Phe], or Dop2-DTyr-DTyr-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-Dcys]-Thr(Bzl)-Tyr-NH 2 3 0 or a pharmaceutically acceptable salt thereof.

H:\MaraR\Keep\Speci\P64463-div-SPECI.doC 7/02/08 00 19 [0150] In a fourth aspect, the invention features a method of eliciting a somatostatin receptor agonist effect in a subject in need thereof, wherein said method comprises administering to said subject an effective amount of a chimeric analogue of the invention, wherein said chimeric analogue comprises a compound according to the formula of Formula (111), (VI) (VII), (VIII), or or a pharmaceutically acceptable salt thereof;, or intermediate compound (14), or or an organic or inorganic salt thereof; and wherein said effective amount is the amount effective to elicit a somatostatin receptor agonist effect 00 in said subject.

101511 In a first embodiment of the fourth aspect, the chimeric analogue comprises any of the compounds listed in Table 1; or a pharmaceutically acceptable salt thereof.

[0152] In a second embodiment of the fourth aspect, the chimeric analogue comprises a compound according to the formula of: Dop2-DPhe-Doc-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop2-DPhe-Doc-DPhe-cyclo[Cys-3 ITyr(Dop2)-DTrp-Lys-Val-Cys] -Thr-NH 2 Ac-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Ac-DLys(Dop2)-DPhe-cyclo [Cys-3 lTyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop3 -DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop5-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclollCys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-DPhe-cyclo [Cys-3 ITyr(Dop2)-DTrp-Lys-Val-CysI-Thr-NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI .doc 7/02/08 20 00 Dop2-Lys(Dop2)-DPhe-cyclo[Cys-3ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 or SDop2-DLys(Dop2)-DPhe-cyclo[Cys-3ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 or a pharmaceutically acceptable salt thereof.

[0153] In a preferred embodiment, the chimeric analogue comprises a compound according to the formula of: Dop2-Lys(Dop2)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2,

O

0Dop2-DLys(Dop2)-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 or 00 Dop2-DPhe-cyclo[Cys-3ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 or a pharmaceutically acceptable salt thereof.

[0154] In a more preferred embodiment of the fourth aspect, the chimeric analog comprises a compound according to the formula of Dop2-Lys(Dop2)-DTyr-DTyrcyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2; or a pharmaceutically acceptable salt thereof. In another more preferred embodiment of the fourth aspect, chimeric analogue comprises a compound according to the formula of Dop2-DLys(Dop2)-cyclo[Cys-Tyr- DTrp-Lys-Abu-Cys]-Thr-NH 2 or a pharmaceutically acceptable salt thereof. In yet another more preferred embodiment of the fourth aspect, chimeric analogue comprises a compound according to the formula of Dop2-DPhe-cyclo[Cys-31Tyr-DTrp-Lys-Thr- Cys]-Thr-NH 2 or a pharmaceutically acceptable salt thereof.

[0155] In a third embodiment of the fourth aspect, the chimeric analogue comprises a compound according to the formula of: Dop2-Lys(Dop2)-DTyr-Tyr-cyclo[DDab-Arg-Phe-Phe-DTrp-Lys-Thr-Phe], Dop2-Tyr-cyclo[DDab-Arg-Phe-Phe-DTrp-Lys-Thr-Phe], or Dop2-DTyr-DTyr-Caeg-cyclo[DCys-3Pal-DTrp-Lys-Dcys]-Thr(Bzl)-Tyr-NH 2 or a pharmaceutically acceptable salt thereof.

[0156] In a fifth aspect, the invention features a method of eliciting both a dopamine receptor agonist effect and a somatostatin receptor agonist effect in a subject in need thereof, wherein said method comprises administering to said subject an effective amount of a chimeric analogue of the invention, wherein said chimeric analogue comprises a compound according to the formula of Formula (III), (VI) (VII), (VIII), or or a pharmaceutically acceptable salt thereof; or H;\MaraR\Keep\Speci\p64463-div-SPECI.doc 7/02/08 00 21 intermediate compound or or an organic or inorganic salt thereof; and wherein said effective amount is the amount effective to elicit both a dopamine and a somatostatin receptor agonist effect in said subject.

101571 In a first embodiment of the fifth aspect, the chimeric analogue comprises any of the compounds listed in Table 1; or a pharmaceutically acceptable salt thereof.

[01581 In a second embodiment of the fifth aspect, the chimeric analogue comprises C a compound according to the formula of: Dop2-DPhe-Doc-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr-NH 2 00Dop2-DPhe-Doc-DPhe-cyclo [Cys-3 ITyr(Dop2)-DTrp-Lys-Val-Cys] -Thr-NH 2 Ac-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Ac-DLys(Dop2)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop3 -DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop5-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, Dop2-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Tin-NH 2 Dop2-Lys(Dop2)-DPhe-cyclollCys-Tyr-DTrp-Lys-Abu-Cys] -Tin-NH 2 Dop2-Lys(Dop2)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Tin-NH 2 Dop5 -Lys(Dop5)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-DPhe-cyclo[Cys-3 ITyr(Dop2)-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Tin-NH 2 Dop2-Lys(Dop2)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 or Dop2-DLys(Dop2)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Tin-NH 2 or a pharmnaceutically acceptable salt thereof.

101591 In a preferred embodiment, the chimeric analogue comprises a compound according to the formula of: Dop2-Lys(Dop2)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, H:\MaraR\Keep\Speci\P64463-div-SPECI .doc '7/02/06 00- 22

O

0 Dop2-DLys(Dop2)-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 or Dop2-DPhe-cyclo[Cys-3ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 or Sa pharmaceutically acceptable salt thereof.

10160] In a more preferred embodiment of the fifth aspect, the chimeric analog comprises a compound according to the formula of Dop2-Lys(Dop2)-DTyr-DTyrcyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 or a pharmaceutically acceptable salt \O thereof. In another more preferred embodiment of the fifth aspect, chimeric analogue

O

Scomprises a compound according to the formula of Dop2-DLys(Dop2)-cyclo[Cys-Tyr-

(N

00 DTrp-Lys-Abu-Cys]-Thr-NH 2 or a pharmaceutically acceptable salt thereof. In yet 0 another more preferred embodiment of the fifth aspect, chimeric analogue comprises a compound according to the formula of Dop2-DPhe-cyclo[Cys-3lTyr-DTrp-Lys-Thr- Cys]-Thr-NH 2 or a pharmaceutically acceptable salt thereof.

[0161] In a third embodiment of the fifth aspect, the chimeric analogue comprises a compound according to the formula of: Dop2-Lys(Dop2)-DTyr-Tyr-cyclo[DDab-Arg-Phe-Phe-DTrp-Lys-Thr-Phe], Dop2-Tyr-cyclo[DDab-Arg-Phe-Phe-DTrp-Lys-Thr-Phe], or Dop2-DTyr-DTyr-Caeg-cyclo[DCys-3Pal-DTrp-Lys-Dcys]-Thr(Bzl)-Tyr-NH 2 or a pharmaceutically acceptable salt thereof.

[0162] In a sixth aspect, the invention features a pharmaceutical composition comprising an effective amount of a compound according to the formula of Formula (III), (VI) (VII), (VIII), or or a pharmaceutically acceptable salt thereof; or intermediate compound or or an organic or inorganic salt thereof; in a pharmaceutically acceptable carrier, wherein said effective amount is the amount effective to elicit a dopamine receptor agonist effect or a somatostatin receptor agonist effect or both in a subject in need thereof.

[0163] In a first embodiment of the sixth aspect, the chimeric analogue comprises any of the compounds listed in Table 1; or a pharmaceutically acceptable salt thereof.

[01641 In a second embodiment of the sixth aspect, the chimeric analogue comprises a compound according to the formula of: Dop2-DPhe-Doc-DPhe-cyclo[Cys-3ITyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop2-DPhe-Doc-DPhe-cyclo[Cys-3ITyr(Dop2)-DTrp-Lys-Val-Cys]-Thr-NH 2 H\MaraR\Keep\Speci\P64463-div-SPECI.doc 7/02/08 00 23 Ac-Lys(Dop2)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Ac-DLys(Dop2)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop3 -DPhe-cyclollCys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop5-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 00 o2LsDp)Dy-yrccoCsTrDr-y-b-y]TrN2 10Dop2-DLys(Dop2) yrr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-Lys(Dop)D-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DPhe-cyclo [Cys-3 ITyr(Dop2)-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclolCys-3 lTyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 or Dop2-DLys(Dop2)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 or a pharmaceutically acceptable salt thereof.

[0165] In a preferred embodiment, the chimeric analogue comprises a compound according to the formula of: Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-DLys(Dop2)-cyclo[ICys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 or Dop2-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 or a pharmaceutically acceptable salt thereof.

[01661 In a more preferred embodiment of the sixth aspect, the chimeric analog comprises a compound according to the formula of Dop2-Lys(Dop2)-DTyr-DTyrcyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 or a pharmaceutically acceptable salt thereof. In another more preferred embodiment of the sixth aspect, chimeric analogue comprises a compound according to the formula of Dop2-DLys(Dop2)-cyclo[Cys-Tyr- DTrp-Lys-Abu-Cys]-Thr-NH 2 or a pharmaceutically acceptable salt thereof. In yet H:\MaraR\Keep\Speci\P64463-div-SPECI .doc 7/02/08 00 24 0 0 another more preferred embodiment of the sixth aspect, chimeric analogue comprises a N compound according to the formula of Dop2-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr- Cys]-Thr-NH 2 or a pharmaceutically acceptable salt thereof.

[01671 In a third embodiment of the sixth aspect, the chimeric analogue comprises a compound according to the formula of: Dop2-Lys(Dop2)-DTyr-Tyr-cyclo [DDab-Arg-Phe-Phe-DTrp-Lys-Thr-Phe], Dop2-Tyr-cyclo [DDab-Arg-Phe-Phe-DTrp-Lys-Thr-Phe], or Dop2-DTyr-DTyr-Caeg-cyclo[DCys-3 Pal-DTrp-Lys-Dcys] -Thr(Bzl)-Tyr-NH 2 00 or a pharmaceutically acceptable salt thereof.

101681 In a seventh aspect, the invention features a method of treating a disease or condition in a subject, said method comprising administering to said subject a therapeutically effective amount of a chimeric analog, wherein said chimeric analog comprises a compound according to the formula of Formula (III), (VI) (VII), (VIII), or any of the compounds listed in Table 1; Dop2-DPhe-Doc-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop2-DPhe-Doc-DPhe-cyclo [Cys-3 ITyr(Dop2)-DTrp-Lys-Val-Cys] -Thr-NH 2 Ac-Lys(Dop2)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, Ac-DLys(Dop2)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys.-Thr-Cys] -Thr-NH 2 Dop3-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop4-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 -Thr-NH 2 Dop2-DPhe-cyclo[Cys-3 ITyr(Dop2)-DTrp-Lys-Val-Cys] -Thr-NH 2 H:\MaraR\Keep\Speci\P64463-diV-SPECI.doc 7/02/08 00- 25

O

SDop2-Lys(Dop2)-DTyr-DTyr-cyclo[Cys-3ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-DPhe-cyclo[Cys-3ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop2-DLys(Dop2)-DPhe-cyclo[Cys-3ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-DTyr-Tyr-cyclo[DDab-Arg-Phe-Phe-DTrp-Lys-Thr-Phe], Dop2-Tyr-cyclo[DDab-Arg-Phe-Phe-DTrp-Lys-Thr-Phe], or \0 Dop2-DTyr-DTyr-Caeg-cyclo[DCys-3Pal-DTrp-Lys-Dcys]-Thr(Bzl)-Tyr-NH 2

O

Sor 00 a pharmaceutically acceptable salt thereof; or intermediate compound (11), 0 10 or or an organic or inorganic salt thereof; and wherein said disease or disorder is selected from the list consisting of a neuroendocrine tumor; a vascular disease; a connective tissue disease; an immune disease; a disorder of the gastrointestinal tract, pancreas, kidney, or liver; a metabolic disease; a cachexia; cancer or a tumor of the lung, breast, prostate, liver, thyroid, blood; a musculoskeletal disorder;a panic disorder; and opioid overdose; and wherein said therapeutically effective amount is the amount effective to treat said disease or disorder in said patient.

[0169] In a first embodiment of the seventh aspect, the neuroendocrine tumor is a neuroendocrine tumor of the pituitary. In a first preferred embodiment, the neuroendocrine tumor of the pituitary is an ACTH-producing tumor. Preferably, the ACTH-producing tumor is Cushing's disease. In a second preferred embodiment, the neuroendocrine tumor of the pituitary is a growth hormone producing tumor.

Preferably, the growth hormone producing tumor is acromegaly. In a third preferred embodiment, the neuroendocrine tumor of the pituitary is a prolactin-producing tumor.

Preferably, the prolactin-producing tumor is a prolactinoma. In a fourth preferred embodiment, the neuroendocrine tumor of the pituitary is hyperprolactinemia or prolactinemia. In a fifth preferred embodiment, the neuroendocrine tumor of the pituitary is thyroid stimulating hormone (TSH) secreting tumor. In a sixth preferred embodiment, the neuroendocrine tumor of the pituitary is "nonfunctioning" pituitary adenoma. In a seventh preferred embodiment, the neuroendocrine tumor of the pituitary is gonadotropinoma.

[0170] In a second embodiment of the seventh aspect, the neuroendocrine tumor is carcinoid tumor. In a preferred embodiment, the carcinoid tumor causes carcinoid H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 7/02/08 00 26

O

0 syndrome. In a third embodiment of the seventh aspect, the neuroendocrine tumor is glucagonoma. In a fourth embodiment of the seventh aspect, the neuroendocrine tumor Sis small cell lung carcinoma. In a fifth embodiment of the seventh aspect, the neuroendocrine tumor is thyroid medullary carcinoma. In a sixth embodiment of the seventh aspect, the neuroendocrine tumor is VIPoma. In a seventh embodiment of the seventh aspect, the neuroendocrine tumor is insulinoma. In an eighth embodiment of O0 the seventh aspect, the disorder of said vascular disease is inappropriate angiogenesis.

O

0In a ninth embodiment of the seventh aspect, the disorder of said vascular disease is 00 restenosis. In a tenth embodiment of the seventh aspect, the disorder of said vascular

O

disease is retinopathy. In a preferred embodiment, the retinopathy is diabetic retinopathy or proliferative retinopathy. In another preferred embodiment, the retinopathy is macular degeneration, preferably, age-related macular degeneration.

10171] In another embodiment of the seventh aspect, the connective tissue disease is scleroderma. In yet another embodiment of the seventh aspect, the immune disease is rheumatoid arthritis. In yet another embodiment of the seventh aspect, the immune disease is inflammation. In yet another embodiment of the seventh aspect, the immune disease is fibrosis. In yet another embodiment of the seventh aspect, the immune disease is Graves' opthalmopathy. In yet another embodiment of the seventh aspect, the immune disease is allograft rejection. In yet another embodiment of the seventh aspect, the disorder of the gastrointestinal tract comprises gastric acid secretion, peptic ulcers, inflammatory bowel disease (IBD), or diarrhea. In a preferred embodiment, the IBD is irritable bowel syndrome or Crohn's disease. In another preferred embodiment, the diarrhea is AIDS related or chemotherapy related or watery diarrhea syndrome. In yet another preferred embodiment, the disorder of the gastrointestinal tract is small bowel syndrome, small bowel obstruction, gastroesophageal reflux, duodenogastric reflux, H.

pylori proliferation, or gastrointestinal bleeding.

[0172] In yet another embodiment of the seventh aspect, the metabolic disease comprises hyperlipidemia, insulin resistance, Syndrome X, obesity, diabetes, or a diabetes-related disease. In a preferred embodiment, the diabetes-related disease 3 0 comprises diabetic nephropathy, diabetic neuropathy, diabetic retinopathy, or gastroparesis.

H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 7/02/08 27

O

0 [0173] In yet another embodiment of the seventh aspect, the cachexia is cardiac cachexia, cancer cachexia, or geriatric cachexia.

1[0174] In yet another embodiment of the seventh aspect, the disease or disorder comprises glioma, anorexia, hypothyroidism, Graves' disease, hyperaldeosteronism, systemic sclerosis, pancreatitis, external and internal pancreatic pseudocysts and ascites, pancreaticocutaneous fistula, nesidoblastosis, hyperinsulinism, gastrinoma, Zollinger- O0 Ellison Syndrome, gastrointestinal hormone secreting tumor, dawn phenomenon,

O

Sdumping syndrome, hyperparathyroidism, Paget's disease, polycystic ovary disease, 00 orthostatic hypotension, postprandial hypotension, portal hypertension, angiopathy, or

O

graft vessel bleeding.

10175] In a first related embodiment of the aspect of the invention disclosed above, the chimeric analog comprises a SSTR-1 agonist and a dopamine receptor agonist; or a pharmaceutically acceptable salt thereof. In a first preferred embodiment, the chimeric analog further comprises a SSTR-2 agonist or a SSTR-3 agonist, or a pharamaceutically acceptable salt thereof, or both.

[0176] In a second preferred embodiment, the chimeric analog further comprises a agonist, or a pharmaceutically acceptable salt thereof. In a third preferred embodiment, the chimeric analog further comprises a SSTR-2 agonist or a SSTR-3 agonist, or a pharmaceutically acceptable salt thereof.

[0177] In a more preferred embodiment, the chimeric analog comprises a SSTR-1 agonist and a dopamine receptor agonist and further comprises a SSTR-2 agonist, a SSTR-3 agonist, and a SSTR-5 agonist, or a pharmaceutically acceptable salt thereof.

[01781 In a second related embodiment of the aspect of the invention disclosed above, the chimeric analog comprises a SSTR-2 agonist and a dopamine receptor agonist; or a pharmaceutically acceptable salt thereof. In a preferred embodiment, the chimeric analog further comprises a SSTR-5 agonist, or a pharmaceutically acceptable salt thereof.

[0179] In a third related embodiment of the aspect of the invention disclosed above, the chimeric analog comprises a SSTR-3 agonist and a dopamine receptor agonist; or a pharmaceutically acceptable salt thereof.

H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 7/02/08 00 28 0 101801 In a fourth related embodiment of the aspect of the invention disclosed above, N the chimeric analog comprises a SSTR-5 agonist and a dopamine receptor agonist; or a pharmaceutically acceptable salt thereof.

101811 In an eighth aspect, the invention features a method of treating acromegaly in a subject in need thereof, wherein said method comprises administering to said subject a therapeutically effective amount of a chimeric analog, wherein said chimeric analog C comprises a compound according to the formula of Formula (111), (VI) (VII), (VIII), or any of the compounds listed in Table 1; 00 Dop2-DPhe-Doc-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop2-DPhe-Doc-DPhe-cyclo[Cys-3 ITyr(Dop2)-DTrp-Lys-Val-Cys]-Thr-NH 2 Ac-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Ac-DLys(Dop2)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop3-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop5-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 -Thr-NH 2 Dop2-DPhe-cyclo [Cys-3 ITyr(Dop2)-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-DPhe-cyclo[Cys-3lTyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-DTyr-Tyr-cyclo [DDab-Arg-Phe-Phe-DTrp-Lys-Thr-Phe], Dop2-Tyr-cyclo [DDab-Arg-Phe-Phe-DTrp-Lys-Thr-Phe], or Dop2-DTyr-DTyr-Caeg-cyc lo [DCys-3 Pal-DTrp-Lys-Dcys]-Thr(Bzl)-Tyr-NH 2 or H!\MaraR\Keep\SpeCi\P64463-div-SPECI.doC 7/02/08 00 29 a pharmaceutically acceptable salt thereof; or intermediate compound (11), or or an organic or inorganic salt thereof;, and the therapeutically effective amount is the amount effective to treat acromegaly in said patient. In a preferred embodiment of this aspect of the invention, the chimeric analog comprises a SSTR-5 agonist and a dopamine receptor agonist. More preferably, the chimeric analog further comprises a SSTR-2 agonist.

[01821 In another preferred embodiment of this aspect, the subject has developed or is at risk of developing acromegaly.

00 101831 In a ninth aspect, the invention features a method of treating prolactinemia in a subject in need thereof, wherein said method comprises administering to said subject a therapeutically effective amount of a chimeric analog, wherein said chimeric analog comprises a compound according to the formula of Formnula (111), (VI) (VII), (VIII), or any of the compounds listed in Table 1; Dop2-DPhe-Doc-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop2-DPhe-Doc-DPhe-cyclo[Cys-3 ITyr(Dop2)-DTrp-Lys-Val-Cys] -Thr-NH 2 Ac-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, Ac-DLys(Dop2)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop3-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop5-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, Dop2-Lys(Dop2)-cycloIICys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-DLys(Dop2)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 -Thr-NH 2 Dop2-DPhe-cyclo [Cys-3 ITyr(Dop2)-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Ht\MaraR\Keep\Speci\P64463-div-SPECI.dOC 7/02/08 00- 30 Dop2-DLys(Dop2)-DPhe-cyclo[Cys-3lTyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 SDop2-Lys(Dop2)-DTyr-Tyr-cyclo[DDab-Arg-Phe-Phe-DTrp-Lys-Thr-Phe], r Dop2-Tyr-cyclo[DDab-Arg-Phe-Phe-DTrp-Lys-Thr-Phe], or Dop2-DTyr-DTyr-Caeg-cyclo[DCys-3Pal-DTrp-Lys-Dcys]-Thr(Bzl)-Tyr-NH 2 or Sa pharmaceutically acceptable salt thereof; or intermediate compound (11), s0 or or an organic or inorganic salt thereof; and the 0therapeutically effective amount is the amount effective to treat prolactinemia in said 00 patient. In a preferred embodiment of this aspect of the invention, the chimeric analog comprises a SSTR-5 agonist and a dopamine receptor agonist. More preferably, the chimeric analog further comprises a SSTR-2 agonist.

[01841 In another preferred embodiment of this aspect, the subject has developed or is at risk of developing prolactinemia.

[0185] In some embodiments, compounds of the invention may include the structure of DopA-Lys(DopA), wherein Lys is L-lysine, unless expressly designated as DLys. A is 1-13, for example, Dopl, Dop2, Dop3, Dop4, Dop5, Dop6, Dop7, Dop8, Dop9, DoplO, Dopl 1, Dopl2, and Dopl3. The structure of a DopA-Lys(DopA), in which A is 2 Dop2-Lys(Dop2)), and in which A is 5 Dop5-Lys(Dop5)), are shown below.

[01861 By "Dopl" is meant a compound having the structure of: \s 0 H N

H

H [01871 By "Dop2" is meant a compound having the structure of:

S

0 H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 7/02/08 31 101881 By "Dop3" is meant a compound having the structure of:

NH

OI 0 0

H

[01891 By "Dop4" is meant a compound having the structure of:

NH

'0 150 gHH [0 1901 By "Dop5" is meant a compound having the structure of:

OH

OH

H 2

N)(

0 101911 By "Dop6" is meant a compound having the structure of: 101921 By "Dop7" is meant a compound having the structure of: H:\MaraR\Keep\Speci\P64463-div-SPECIdoc 7/02/08 32 [0193] By "Dop8" is meant a compound having the structure of: [0194] By "Dop9" is meant a compound having the structure of: HN

N

0 [01951 By "Dopi 0" is meant a compound having the structure of: 10196] By "Dopl 1" is meant a compound having the structure of:

OH

N

10197] By "Dopl2" is meant a compound having the structure of: H:\araR\Keep\Speci\p64463-div-SPECIdoc 7/02/08 33

HOH

101981 By "Dop13 is meant a compound having the structure of: 101991 Lys(Dop2) has the structure of: 102001 Dop2-Lys(Dop2) has the structure of: 102011 Lys(Dop5) has the structure of: H:\MaraR\Keep\Speci\P64463-div-SPECIdoC 7/02/08 00 34 O0

N

O o O

H

O o OO 00 O [0202] Dop5-Lys(Dop5) has the structure of: 0o 0

O

N

0 H 0

H

10203] By "Alkyl" is meant a hydrocarbon group containing one or more carbon atoms, where multiple carbon atoms if present are joined by single bonds. The alkyl hydrocarbon group may be straight-chain or contain one or more branches or cyclic groups.

[0204] By "Substituted alkyl" is meant an alkyl wherein one or more hydrogen atoms of the hydrocarbon group are replaced with one or more substituents selected from the group consisting of halogen fluorine, chlorine, bromine, and iodine), -OH, -CN, -SH, -NH 2

-NHCH

3

-NO

2

-CI-

2 alkyl substituted with 1 to 5 halogens,

-CF

3

-OCH

3

-OCF

3 and -(CH 2 )04-COOH. In different embodiments 1, 2, 3 or 4 substituents are present. The presence of -(CH 2 )04-COOH results in the production of H:\MaraR\Keep\Speci\P64463-div-SPECI.doC 7/02/08 00 35

OO

0 an alkyl acid. Examples of alkyl acids containing, or consisting of, -(CH 2 )o-4-COOH include 2-norbornane acetic acid, tert-butyric acid and 3-cyclopentyl propionic acid.

[0205] By "Heteroalkyl" is meant an alkyl wherein one of more of the carbon atoms in the hydrocarbon group are replaced with one or more of the following groups: amino, amido, or carbonyl. In different embodiments 1 or 2 heteroatoms are present.

1 [02061 By "Substituted heteroalkyl" is meant a heteroalkyl wherein one or more \O hydrogen atoms of the hydrocarbon group are replaced with one or more substituents 0 Sselected from the group consisting of halogen, fluorine, chlorine, bromine, and 00 iodine), -OH, -CN, -SH, -NH 2

-NHCH

3

-NO

2

-C

i 2 alkyl substituted with 1 to halogens, -CF 3

-OCH

3

-OCF

3 and -(CH2)o-4-COOH. In different embodiments 1, 2, 3 or 4 substituents are present.

[0207] By "Alkenyl" is meant a hydrocarbon group made up of two or more carbons where one or more carbon-carbon double bonds are present. The alkenyl hydrocarbon group may be straight-chain or contain one or more branches or cyclic groups.

[0208] "Substituted alkenyl" refers to an alkenyl where one or more hydrogens are replaced with one or more substituents selected from the group consisting of halogen fluorine, chlorine, bromine, and iodine), -OH, -CN, -SH, -NH 2

-NHCH

3

-NO

2 -Ci- 2 alkyl substituted with 1 to 5 halogens, -CF 3

-OCH

3

-OCF

3 and -(CH 2 )o-4-COOH.

In different embodiments 1, 2, 3 or 4 substituents are present.

[0209] By "Alkynyl" is meant to a hydrocarbon group made up of two or more carbons where one or more carbon-carbon triple bonds are present. The alkynyl hydrocarbon group may be straight-chain or contain one or more branches or cyclic groups.

[0210] By "Substituted alkynyl" is meant an alkynyl where one or more hydrogens are replaced with one or more substituents selected from the group consisting of a halogen fluorine, chlorine, bromine, and iodine), -OH, -CN, -SH, -NH 2

-NHCH

3

-NO

2 -C1-2 alkyl substituted with 1 to 5 halogens, -CF 3

-OCH

3

-OCF

3 and

-(CH

2 )o-4-COOH. In different embodiments 1, 2, 3 or 4 substituents are present.

[0211] By "Aryl" is meant an optionally substituted aromatic group with at least one ring having a conjugated pi-electron system, containing up to two conjugated or fused ring systems. Aryl includes carbocyclic aryl, heterocyclic aryl and biaryl groups.

Preferably, the aryl is a 5 or 6 membered ring. Preferred atoms for a heterocyclic aryl H:\MaraR\Keep\Speci\P64463-div-SPECI.doC 7/02/08 00 36 00 are one or more sulfur, oxygen, and/or nitrogen. Examples of aryl include phenyl, I-naphthyl, 2-naphthyl, indole, quinoline, 2-imidazole, and 9-anthracene. Aryl substituents are selected from the group consisting of -C14 alkyl, -C 1 -4 alkoxy, halogen fluorine, chlorine, bromine, and iodine), -OH, -CN, -SH, -NH 2

-NO

2 -Cl-2 alkyl substituted with 1 to 5 halogens, -CF 3

-OCF

3 and -(CH 2 )04-COOH. In different embodiments the aryl contains 0, 1,2, 3, or 4 substituents.

[0212] By "Acyl" is meant where R" is alkyl, substituted alkyl, heteroalkyl, substituted heteroalkyl, alkenyl, substituted alkenyl, alkynyl, substituted oO alkynyl, aryl, alkylaryl, or substituted alklyaryl and X' is H or absent.

10213] By "Arylalkyl" or "alkylaryl" is meant an "alkyl" joined to an "aryl".

10214] By "Abu" is meant a-aminobutyric acid.

102151 By "Aepa" is meant 4-(2-aminoethyl)-1-carboxy methyl-piperazine, represented by the structure: 0 [0216] By "Aib" is meant a-aminoisobutyric acid.

[0217] By "Ala" or A" is meant alanine.

102181 By "fl-Ala" is meant beta-alanine.

[0219] By "Arg" or is meant arginine.

[0220] By "Asn" or is meant asparagine.

[02211 By "Asp or is meant aspartic acid.

[02221 By "Caeg" is meant N-(2-aminoethyl)-N-(2-cytosinyl-1-oxo-ethyl)-glycine, represented by the structure:

NH

2

N

0 N 3 -N

H

H:\MaraR\Keep\Speci\P64463-div-SPECI.dOC 7/02/08 37 102231 By "Cys" or is meant cysteine.

[02241 By "Dab" is meant 2,4-diaminobutyric acid.

[02251 By "Doc" is meant 8-amino-3, 6-dioxaoctanoic acid, represented by the structure H9 [02261 By "Gin" or is meant giutamine.

[02271 By "Giu" or is meant giutamic acid.

102281 By "Gly" or is meant glycine.

[02291 By "His" or is meant histidine.

[02301 By "Ile" or is meant isoleucine.

[02311 By "Leu" or is meant leucine.

[02321 By "Lys" or K" is meant iysine.

[02331 By "Met" or "MWis meant methionine.

[02341 By "IlNal"is meant j-(l-naphthyi)alanine.

[02351 By "2Na"is meant j-(2-naphthyl)aianine.

[0236] By "Nle"is meant norleucine.

102371 By "Orn"is meant ornithine.

[02381 By "2Pai"is meantfi3-(2-pyridinyi)aianine.

[02391 By "3Pai"is meant fi-(3 -pyridinyi)alanine.

[02401 By "4Pai"is meantfi3-(4-pyri dinyi)al anine.

[02411 By "Phe" or "F"is meant phenyialanine.

[02421 By "Pro" or "P"is meant proiine.

[02431 By "Ser" or "S"is meant serine.

[02441 By "Thr" or is meant threonine.

[0245] By "Thr-oi" is meant threoninol, represented by the structure:

'~OH

OH

NZ

I

H

[02461 By "Val" or is meant valine.

H:\MaraR\Keep\Speci\P64463-div-SPECI doC 7/02/08 8[0247] By "(N-Me)Trp" is meant N-cc-methyl-tryptophan.

[02481 Certain other abbreviations used herein are defined as follows: 102491 By "Ac" is meant acetyl.

__[02501 By "Boc" is meant tert-butyloxycarbonyl.

10251] By "BAl" is meant benzyl.

[02521 By "DCM" is meant dichioromethane.

[02531 By "DIC" is meant N, N-diisopropylcarbodiimide.

[02541 By "DIEA" is meant diisopropylethyl amine.

00102551 By "Dmnab" is meant 4-{N-(1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3methylbutyl)-amino} benzyl.

[02561 By "DMAP" is meant 4-(dimethylamino)pyridine.

102571 By "DMF is meant dimethylformamide.

[0258] By "DNP" is meant 2,4-dinitrophenyl.

[02591 By "Fmoc" is meant Fluorenylmethyloxycarbonyl.

102601 By "HBTU" is meant 2-(1H-benzotriazole-I-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate.

[0261] By "cHex" is meant cyclohexyl.

[02621 By "HOAT" is meant O-(7-azabenzotriazol-1I-yl)- 1, 1,3,3-tetramethyluronium hexafluorophosphate.

[02631 By "HOBt" is meant I1-hydroxy-benzotriazole.

[0264] By "Mint" is meant 4-methoxytrityl.

102651 By "NMP" is meant N-methylpyrrolidone.

102661 By "Pbf' is meant 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl.

102671 By "tBu" is meant tert-butyl.

[02681 By "TIS" is meant triisopropylsi lane.

[02691 By "TOS" is meant tosyl.

102701 By "trt" is meant trityl.

[02711 By "TFA" is meant trifluoro acetic acid.

[02721 By "TFFH" is meant tetramethyifluoroforamidinium hexafluorophosphate.

102731 By "Trp" or is meant tryptophan.

10274] By "Tyr" or is meant tyrosine.

102751 By "31Tyr" is meant 3-iodo-tyrosine.

H:\MaraR\Keep\Speci\P64463-div-SPECI.doC 7/02/08 00 39 0 O [02761 3ITyr(Dop2) has the structure of: I O 7 0 H

NH

0

C-IN

00 102771 By a "somatostatin receptor agonist" is meant a compound that has a high binding affinity Ki of less than 100 nM, or preferably less than 10 nM, or more preferably less than 1 nM) for a somatostatin receptor as defined by the receptor binding assay described below), such as any of the different subtypes: SSTR-1, SSTR-2, SSTR-3, SSTR-4, and SSTR-5, and elicits a somatostatin-like effect; for example, in an assay for the inhibition of cAMP intracellular production.

[02781 By a "somatostatin selective agonist" is meant a somatostatin receptor agonist which has a higher binding affinity lower Ki) for one somatostatin receptor subtype than for any other somatostatin receptor subtype, such as, for example, a somatostatin SSTR-2 selective agonist.

[0279] By a "dopamine receptor agonist" is meant a compound that has a high binding affinity Ki of less than 100 nM, or preferably less than 10 nM, or more preferably less than 1 nM) for a dopamine receptor as defined by the receptor binding assay described below), such as any of the different subtypes: Dl, D2, D3, D4, and D5 receptors.

Detailed Description [0280] The invention features somatostatin-dopamine chimeric analogs and methods relating to their therapeutic use for the treatment of neoplasia, acromegaly, and other conditions.

[0281] Various somatostatin receptors (SSTR's) have been isolated SSTR-I, SSTR-2, SSTR-3, SSTR-4, and SSTR-5). Somatostatin agonists are those compounds SSTR-2, SSTR-3, SSTR-4, and SSTR-5). Somatostatin agonists are those compounds H:\MaraR\Keep\speci\P64463-div-SPECI.doc 7/02/08 40 00 0that bind to at least one SSTR SSTR-1 agonist, SSTR-2 agonist, SSTR-3 agonist, SSTR-4 agonist or a SSTR-5 agonist).

[02821 Further examples of somatostatin agonists are those covered by formulae or those specifically recited in the publications set forth below, each of which is hereby incorporated by reference in its entirety.

PCT Application No. WO 03/057214 (2003) U.S. Application No. 20030191134 (2003) SU.S. Application No. 20030083241 (2003) 00 PCT Application No. WO 02/10215 (2002) 0 10 U.S. Patent No. 6,316,414 (2001) PCT Application No. WO 99/22735 (1999) PCT Application No. WO 99/2273508100 (1999) PCT Application No. WO 98/08492100 (1998) PCT Application No. WO 98/4492185 (1998) PCT Application No. WO 98/45285 (1998) PCT Application No. WO 98/44922 (1998) EP Application No. P5 164 EU (Inventor: G. Keri); Van Binst, G. et al. Peptide Research 5:8 (1992); Horvath, A. et al. Abstract, "Conformations of Somatostatin Analogs Having Antitumor Activity", 22nd European peptide Symposium, September 13-19, 1992, Interlaken, Switzerland; PCT Application No. WO 91/09056 (1991); EP Application No. 0 363 589 A2 (1990); U.S. Patent No. 4,904,642 (1990); U.S. Patent No. 4,871,717 (1989); U.S. Patent No. 4,853,371 (1989); U.S. Patent No. 4,725,577 (1988); U.S. Patent No. 4,684,620 (1987); U.S. Patent No. 4,650,787 (1987); U.S. Patent No. 4,603,120 (1986); U.S. Patent No. 4,585,755 (1986); EP Application No. 0 203 031 A2 (1986); U.S. Patent No. 4,522,813 (1985); H:\MaraR\Keep\Speci\P64463-div-SPECI.doC 7/02/08 00- 41-

O

U.S. Patent No. 4,486,415 (1984); Patent No. 4,485,101 (1984); U.S. Patent No. 4,435,385 (1984); U.S. Patent No. 4,395,403 (1983); U.S. Patent No. 4,369,179 (1983); U.S. Patent No. 4,360,516 (1982); U.S. Patent No. 4,358,439 (1982); OU.S. Patent No. 4,358,214 (1982); 00 U.S. Patent No. 4,316,890 (1982); U.S. Patent No. 4,310,518 (1982); U.S. Patent No. 4,291,022 (1981); U.S. Patent No. 4,238,481 (1980); U.S. Patent No. 4,235,886 (1980); U.S. Patent No. 4,224,199 (1980); U.S. Patent No. 4,211,693 (1980); U.S. Patent No. 4,190,648 (1980); U.S. Patent No. 4,146,612 (1979); U.S. Patent No. 4,133,782 (1979); U.S. Patent No. 5,506,339 (1996); U.S. Patent No. 4,261,885 (1981); U.S. Patent No. 4,728,638 (1988); U.S. Patent No. 4,282,143 (1981); U.S. Patent No. 4,215,039 (1980); U.S. Patent No. 4,209,426 (1980); U.S. Patent No. 4,190,575 (1980); EP Patent No. 0 389 180 (1990); EP Patent No. 0 505 680 (1982); EP Patent No. 0 083 305 (1982); EP Patent No. 0 030 920 (1980); PCT Application No. WO 88/05052 (1988); PCT Application No. WO 90/12811 (1990); PCT Application No. WO 97/01579 (1997); H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 7/02/08 00 42 00 O PCT Application No. WO 91/18016 (1991); U.K. Application No. GB 2,095,261 (1981); and SFrench Application No. FR 2,522,655 (1983).

[0283] Note that for all somatostatin agonists described herein, each amino acid residue represents the structure of-NH-C(R)H-CO-, in which R is the side chain

CH

3 for Ala). Lines between amino acid residues represent peptide bonds that join the 0 amino acids. Also, where the amino acid residue is optically active, it is the L-form Sconfiguration, unless the D-form is expressly designated. For clarity, disulfide bonds oO disulfide bridge) that exist between two free thiols of Cys residues are not shown.

Abbreviations of the common amino acids are in accordance with IUPAC-IUB recommendations.

Synthesis of Somatostatin Agonists [0284] The methods for synthesizing peptide somatostatin agonists are well documented and are within the ability of a person of ordinary skill in the art. For example, peptides are synthesized on Rink amide MBHA resin dimethoxyphenyl-Fmoc-aminomethyl)-phenoxyacetamido-norleucyl-MBHA resin) using a standard solid phase protocol of Fmoc chemistry. The peptide-resin with free amino functional at the N-terminus is then treated with the corresponding compound containing dopamine moiety. The final product is cleaved off from resin with TFA water/triisopropylsilane (TIS) mixture.

[0285] For example, synthesis of H-D-Phe-Phe-Phe-D-Trp-Lys-Thr-Phe-Thr-NH 2 can be achieved by following the protocol set forth in Example I of European Patent Application 0 395 417 Al. The synthesis of somatostatin agonists with a substituted Nterminus can be achieved, for example, by following the protocol set forth in PCT Publication No. WO 88/02756, PCT Publication No., WO 94/04752, and/or European Patent Application No. 0 329 295.

[02861 Peptides can be and were cyclized by using iodine solution in MeOH/water and purified on C 18 reverse-phase preparative HPLC, using acetonitrile- 0.1%TFA/water-0. I%TFA buffers. Homogeneity was assessed by analytical HPLC and mass spectrometry and determined to be >95% for each peptide.

H:\araR\Keep\Speci\P64463-div-SPECI.doC 7/02/08 43 00 0 [0287] Certain uncommon amino acids were purchased from the following vendors: Fmoc-Doc-OH and Fmoc-AEPA-OH were purchased from Chem-Impex International, SInc. (Wood Dale, IL, USA). Fmoc-Caeg (Bhoc)-OH was purchased from PerSeptive Biosystems (Framingham, MA, USA). Bhoc stands for benzhydryloxycarbonyl.

Synthesis of Dopamine Agonists 0 [0288] The methods for synthesizing many dopamine agonists are also well

O

O documented and are within the ability of a person of ordinary skill in the art. Further 00 synthetic procedures are provided in the following reaction schemes and examples.

O

O

H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 7/02/08 44 Scheme 1 (Cl 1 4)CHO, NaBH 4 Scheme 2 I l1. MsCI-pyridine 1I 2. CH 3

C(O)SH

hydrolysis, OH- H:\maraR\IKeep\speci\P64463-diV-SPECI .doc 7/02/08 45 Scheme 3: Base (CR7RS) 0o-,0 Scheme 4: N,N'-dissuccinimidyl carbonate Scheme N, N'-d issuccin im idyl carbonate H:\MaraR\Keep\Speci\P64463-div-SPECI.doC 7/02/08 46 Scheme 6: oxidation Scheme 7: oxidation H:\MaraR\Keep\Speci\P64463-div-SPECI.doC 7/02/08 47 Scheme 8: HN 'f SH 1) Boc 2

O/DCM

2) Ac 2 O/Base 3)50% TFA in 0CM H2N 'KS S "r R5NCS H H R5-N YN

S

0 011HN

SI

hydrolysis 19 O H R 5 N f 1 0 Scheme 9: H2N On0H 1) Boc 2 O/DCM HN -f 0Y 2) Ac 2 O/Base 0 3)50% TFA in 0CM R5NCS R5 -NY S 0

OH-

hydrolysis OH R5-N.- In0- OH 0 HA\maraR\Keep\Speci\P64463-div-SPECIdoc 7/02/08 48 Scheme 1)BODMR5NCS H 0I

H

2 N )BocOCM

H

2 N~J. .CH 3 R jN" I 2) MeOH/DIC/DMAP/pyridine I 3) 50% TFA in DCM IHgO HN

R

00 0 N -RI 0

H

hydrolysis with base or enzymatic I hydrolysis H esterase) heat 0 R5 -N =tN n C 0 7 np HN 18 (see Scheme 11) 19' (see Scheme 11) H:\maraR\Keep\Speci\P64463-diV-SPECI .doc 7/02/08 49 00 00 Scheme 1: HN'

R

OH

0 1) BrCH 2 C(O)OEtIBase 2) Hydrolysis, OHR Scheme 12: HN f 0< Base (C R9R 10 00 N 0 N-Rl 1, H H:\MaraR\Keep\Speci\P64463-div-SPECI .doc 7/02/08 so Scheme 13: 0 N, N'-disuccinimidyl carbonate Scheme 14: HN' R H R5 0

O

o' N411n ,O-N 1 0 N, N'-disuccinimidyl carbonate Scheme 1) Br-CH 2

-COOCH

3 2) Hydrolysis H: \MaraR\Keep\Speci\P64463-div-SPECI .doc 7/02/08 51 00 00 Scheme I Reduction Ra-Ni or DMF-pyridine/Pd-C, H2 Lysergol Dihydrolysergol R'COCI/pyridine/DMAP CNBr 2) Zn-dust or Ra-Ni/H 2 3) R-I/K 2 C0 3 4) OH-

R=C

15 alkyl, allyl, or alkenyl 1) MsCI/pyridine 2) HS(CH 2 )PC0 2

R

1 1) OR 2) H 3 0+ Compounds 7, and 8' can be synthesized using the synthetic scheme above:

OH

OH

H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 7/02/08 52 Scheme 11 H ,N K

H

BOC

2 0 base

I

H 2N

H

IBOC

2 OI13ase Boc hydrolysis

DIC/DCM

Base

R"'-HN

1) H+ 2) BrCH 2

CO

2

BZI

3) R NCO 4. or enzymatic hydrolysis esterase)

H

Where R" and R" are, independently, H or C 1 alkyl H:\MaraR\Keep\Speci\P64463-div-SPECIdOC 7/02/08 53 Scheme III 1) MsCI/pyridine 2) 0 04N:

NK

0 3) NH 2

NH

2

H

2 0 (CR7R8) 0- o (111) \:maraR\Keep\Speci\P64463-div.SPECI .doc 7/02/08 54 Scheme IV: -1ACH 2

),,CO

2

H

Partially protected somnatostatin ligand on resin or in solution 1) couple 2) deprotect and cleave (ligand on resin) or deprotect (ligand in solution) (From Scheme 1) .4CH 2 ),co-Somatostatin IDerivative

H

H- N

H

)7 N Partially protected somatostatin ligand on resin or H in solution

H",I

I 1) couple X- N H 2) deprotect and cleave (ligand on resin) (II) or deprotect (ligand in solution) (From Scheme 11) R"-HN 4nN 0- Somatostatin Derivative H:\MaraR\Keep\Speci\P64463-divSPECI.doc 7/02/08 55 Scheme V: (11l) (From Scheme 111) Partially protected somatostatin ligand on resin or in solution 1) couple 2) deprotect and cleave (ligand on resin) or deprotect (ligand in solution)

(CR

7 R.-CO-Somatostatin Derivative H:\MaraR\Keep\Speci\P64463-div-SPECI.dOC 7/02/08 56 Scheme VI:

OH

00 Curtius reaction N, NA-disuccin im idylI carbonate/base I 0 1) Sarcosine/base F 2) H- H:\MaraR\Keep\Speci\P64463-div-SPECI .doc 7/02/08 00 57 0 0 Synthesis of Somatostatin-Dopamine Chimers [0289] Somatostatin-dopamine chimers may be synthesized according to the Sfollowing reaction schemes and examples. Starting material and intermediates for such compounds are commercially available or are prepared using standard methods, e.g., see Pharmazie 39, 537 (1984); collect Czech. Chem. Commun. 33, 577 (1966); Helv.

Chim. Acta 32, 1947, (1949), U.S.P. 5,097,031; USP 3,901,894; EP 0003667; and USP 0 4,526,892. Methods for the synthesis of peptides are known to the skilled artisan O see Stewart et al., Solid Phase Synthesis, Pierce Chemical, 2 nd Ed. 1984; G.A. Grant; 00 Synthetic peptide; WH., Freenand Co., New York, 1992; M. Bodenszky A. Bodanszky, The Practice of Peptide Synthesis, Spring Venlag. N.Y. 1984).

[0290] Other somatostatin-dopamine chimers that suppress growth hormone and prolactin secretion and are useful in the treatment of acromegaly are described in Saveanu et al. Clin. Endocrin. and Metab. 87:5545-5552, 2002), hereby incorporated by reference.

[0291] The following examples are provided to illustrate the invention. They are not meant to limit the invention in any way.

Example 1: Dop2-DLys(Dop2)-DPhe-cyclo[Cys-3ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 [0292] The Dop2-DLys(Dop2)-DPhe-cyclo[Cys-3ITyr-DTrp-Lys-Thr-Cys]-Thr-

NH

2 peptide was automatically synthesized on an ACT 396 peptide synthesizer (Advanced ChemTech, Louisville, KY) using Fluorenylmethyloxycarbonyl (Fmoc) chemistry. A RINK AMIDE 4-methylbenzylhydrylamine (MBHA) resin (Novabiochem., San Diego, CA) with substitution of 0.66 mmol/g was used (sub: 0.66 mmol/g, 76 mg, 50 umol scale). The Fmoc amino acids used are Fmoc-DTrp(Boc)-OH, Fmoc-Lys(Boc)-OH, Fmoc-Thr(But)-OH, Fmoc-DPhe-OH, Fmoc-Cys(Trt)-OH, and Fmoc-DLys(Dde))-OH from NOVABIOCHEM (San Diego, CA) and Fmoc-3ITyr-OH from CHEM-IMPEX INTERNATIONAL, Inc. (Wood Dale, IL). The synthesis was carried out on a 50 pmol scale. For each reaction cycle, the ACT 396 peptide synthesizer was programmed to perform: washing with N-methylpyrrolidone (NMP) twice; removing Fmoc protecting group with 20% piperidine in NMP for 1 X 5 min and 1 X 25 min; washing with NMP twice; and double coupling with 4 X fold excess of Fmoc protected amino acid (0.20 mmol), HOBt (0.2 mmol), and N, N'- ).\MaraR\Kcep\Speci\P'C4463-dv-SPECI.doc 7/02/08 00- 58

O

0 diisopropylcarbodiimide (DIC) (0.2 mmol) in N,N-dimethylformamide (DMF) for 1 hour per coupling. The resin was coupled successively according to the sequence.

r[02931 After the peptide chain was assembled, the Fmoc group was removed and the resin was washed completely using NMP and dichloromethane (DCM). The resin was transferred into a reaction vessel on a shaker and treated with 2% hydrozine in DMF for S2 X 30 minutes to remove Dde protecting group in the side chain of DLys. After O0 washing successively with DMF, MeOH and DCM, the resin was shaken overnight with

O

SDop2-OH (54 mg, 3.0 eq), bromo-tris-pyrrolidino-phosphonium hexafluorophosphate 00 (PyBrop, 82 mg, 3.4 eq), 1-hydroxy-7-azabenzotriazole (HOAT, 0.4 mg, 3.0 eq),

O

pentalflurophenol (18.4 mg, 4 eq), DMAP (0.25 mL of 0.1 M in DMF, 1.0 eq) and diisopropylethyl amine (DIEA) (53 p.L, 4 eq).

[0294] After washing successively with DMF, MeOH and DCM, the resin was treated with a mixture of TFA (4.75 mL), H 2 0 (0.4 mL), and triisopropylsilane (TIS, 0.425 mL) for 2 hours. The resin was removed by filtration. The filtrate was poured into 70 mL of ether. The precipitate formed was filtered off and washed thoroughly with ether. This crude product was dissolved in 5 mL of aqueous acetic acid solution (water/acetic acid The solution was then diluted with 50 mL of H 2 0 and 20 mL of acetonitrile, to which was added, dropwise, iodine in methanol until the solution acquired a sustained yellow hue. The solution was stirred slowly for 1 hour and the reaction was terminated by adding aqueous Na 2

S

2 0 3 solution. The crude product was purified on reverse-phase preparative HPLC using a column of C 18 DYNAMAX- 100Ao (4 x 43 cm, Varian, Walnut Creek, CA). The column was eluted with a liner gradient from 90% A and 10% B to 60% A and 40% B in an hour where A was 0.1% TFA in water and B was 0.1% TFA in acetonitrile. Fractions containing a major component by ultraviolet (UV) absorption were pooled and lyophilized. The purity was 95.7% based on an analytical HPLC analysis. Electro-spray ionization mass spectrometry (ESI mass) analysis gave the molecular weight at 1982.6 (in agreement with the calculated molecular weight of 1983.3).

Example 2: Dop2-DPhe-Doc-DPhe-cyclo[Cys-3ITyr(Dop2)-DTrp-Lys-Val-Cys]-Thr-

NH

2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 7/02/08 00- 59

O

100295] The Dop2-DPhe-Doc-DPhe-cyclo[Cys-3ITyr(Dop2)-DTrp-Lys-Val-Cys]- Thr-NH 2 compound was synthesized substantially according to the procedure described Sfor the synthesis of Dop2-DLys(Dop2)-DPhe-cyclo[Cys-3ITyr-DTrp-Lys-Thr-Cys]- Thr-NH 2 (as described above in Example 1) with the following changes. After the assembly of the peptide chain, the resin was transferred into a reaction vessel on a Sshaker and treated with 25% piperidine in DMF for 30 minutes to remove the Fmoc \O protecting group at the N-terminus. After washing successively with DMF, MeOH and

O

SDCM, the resin was shaken overnight with Dop2-OH (3.0 eq), PyBrop (3.4 eq), HOAT 00 (3.0 eq), DMAP (1.0 eq) and DIEA (4 eq). After cleavage and purification, the desired

O

product was found to have a purity of 95% based on an analytical HPLC analysis. ESI mass analysis gave the molecular weight at 2145.9 (in agreement with the calculated molecular weight of 2145.6).

Example 3: Dop2-Lys(Dop2)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-

NH

2 [0296] The titled compound was synthesized substantially according to the procedure described for the synthesis of Dop2-DPhe-Doc-DPhe-c[Cys-3ITyr(Dop2)- DTrp-Lys-Val-Cys]-Thr-NH 2 (described above in Example 2) except that Fmoc- Lys(Fmoc)-OH was used for the coupling of the last Lys residue at the N-terminus. The product was found to be homogenous and the purity was 93.9% by HPLC. ESI mass analysis gave the molecular weight at 2020.9 (in agreement with the calculated molecular weight of 2020.1).

Example 4: Dop2-DPhe-cyclo[Cys-3ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 [0297] The titled compound was synthesized substantially according to the procedure described for the synthesis of Dop2-DPhe-Doc-DPhe-c[Cys-3ITyr(Dop2)- DTrp-Lys-Val-Cys]-Thr-NH 2 (described above in Example The purity of the final product was 93.9% based on an analytical HPLC analysis. ESI mass analysis gave the molecular weight at 1514.50 (in agreement with the calculated molecular weight of 1514.63).

Example 5: Dop2-DLys(Dop2)-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 7/02/08 00 60 0O 0 The titled compound was synthesized substantially according to the procedure described for the synthesis of Dop2-DPhe-Doc-DPhe-c[Cys-3ITyr(Dop2)-DTrp-Lys- SVal-Cys]-Thr-NH 2 (described above in Example 2) except that Fmoc-DLys(Fmoc)-OH was used for the coupling of the last Lys residue at the N-terminus. The product was found to be homogenous and the purity was 99.9% by HPLC. ESI mass analysis gave the molecular weight at 1693.6 (in agreement with the calculated molecular weight of \O 1694.23).

O

O

00 Example 6: Synthesis of intermediate compound (3) OH O0 O0 HO 0 N -N H 2 HH H OH 0 10298] A mixture of R(-)norapomorphine compound 1 (from Sigma, 200 mg, 0.79 mmol) and p-toluenesulfonic acid monohydrate (451 mg, 2.37 mmol) in acetone mL) is stirred at room temperature overnight. The solvent is removed under reduced pressure. The residue is dissolved in methylene chloride (30 mL) and washed with saturated NaHCO 3 aqueous solution (2 times) and brine (2 times), dried over anhydrous MgSO 4 filtered, and concentrated in vacuo. The residue is purified by using column chromatography on silica, yielding acetonide- R(-)norapomorphine, yielding compound 2.

[0299] To a mixture of compound 2 (167 mg, 0.57 mmol) and N,Ndiisopropylethylamine (219 mg, 1.7 mmol) in methylene chloride (20 mL) is added dropwise bromoacetic acid (236 mg, 1.7 mmol) at 0 OC. The mixture is then warmed to room temperature and stirred for 6 hours. The solution is washed with brine (2 times), dried over anhydrous MgSO 4 filtered, and concentrated in vacuo. The residue is purified by using column chromatography on silica, yielding intermediate compound 3.

Example 7: Synthesis of intermediate compound (6) I O H i (LUL L S r i S- 00 61 0 ("1 S[03001 The mixture of R(-)norapomorphine 4 (200 mg, 0.748 mmol), 2- Smethylpropene (83.9 mg, 1.50 mmol), and a catalytic amount of concentrated H 2 S0 4 in

CH

2 C1 2 (20 mL) is stirred at room temperature overnight. The solution is washed with saturated NaHCO 3 in aqueous solution (2 times) and brine (2 times), dried over anhydrous MgSO 4 filtered, and concentrated in vacuo. The residue is purified by using O column chromatography on silica, yielding compound S[03011 To a mixture of compound 5 (150 mg, 0.486 mmol) and N,N- 00 diisopropylethylamine (188 mg, 1.46 mmol) in methylene chloride (20 mL) is added dropwise bromoacetic acid (203 mg, 1.46 mmol) at 0 OC. The mixture is then warmed to room temperature and stirred for 6 hours. The solution is washed with brine (2 times) and dried over anhydrous MgSO 4 filtered, and concentrated in vacuo. The residue is purified by using column chromatography on silica, yielding intermediate compound 6.

Example 8: Synthesis of intermediate compound (11) NH N

OH

H

H

11 [0302] To a mixture of indolone 10 (WO 9415918, 218 mg, 1.00 mmol) and N,Ndiisopropylethylamine (258 mg, 2.0 mmol) in methylene chloride (20 mL) is added 4iodobutyric acid (214 mg, 1.0 mmol). The resulting solution is stirred at room temperature overnight. The solution is concentrated in vacuo. The residue is purified by using column chromatography on silica, yielding intermediate compound 11.

Example 9: Synthesis of intermediate compound (14) H \MaraR\Keep\Speci\P64463-div-SPECI.doc 7/02/08 00 62 00

O

O

OH 0 12 13 14 O [0303] To a mixture of 1-adamantanamine hydrochloride 12 (Aldrich, 187 mg, 1.00 CN mmol) and N,N-diisopropylethylamine (387 mg, 3.0 mmol) in methylene chloride 00 mL) is added 4-iodobutyric acid (214 mg, 1.0 mmol). The resulting solution is stirred at C room temperature overnight. The solution is washed with brine (2 times), dried over anhydrous MgSO 4 filtered, and concentrated in vacuo. The residue is purified by using column chromatography on silica, yielding compound 13.

103041 To a solution of compound 13 (190 mg, 0.8 mmol) in dioxane (6 mL) and water (3 mL) is added IN NaOH (1.0 mL) at 0 OC. To the resulting solution is added di-tert-butyl dicarbonate (192 mg, 0.88 mmol) over 30 min. The mixture is stirred at room temperature for 12 hours. Dioxane is removed under reduced pressure. To the resulting water solution is added ethyl acetate. The pH of the solution is adjusted to about pH 3 by adding 0.2 N HCI solution at 0 OC. The organic layer is separated, washed with water (twice), dried over anhydrous MgSO 4 filtered, and concentrated in vacuo. The residue is purified by using column chromatography on silica, yielding intermediate compound 14.

Example 10: Synthesis of intermediate compound (18) o H 1H OH NN N HO o o o0 O 0 OH OH 0 CH 0 15 16 17 18 10305] The mixture of fenoldopam 15 (from Sigma, 306 mg, 1.00 mmol) and ptoluenesulfonic acid monohydrate (476 mg, 2.50 mmol) in acetone (30 mL) is stirred at room temperature overnight. The solvent is removed under reduced pressure. The H:\MaraR\Keep\Speci\p64463-di.SPECI doC 7/02/08 00 63

O

0residue is dissolved in methylene chloride (30 mL) and washed with saturated NaHCO 3 Saqueous solution (2 times) and brine (2 times), dried over anhydrous MgSO 4 filtered, Sand concentrated in vacuo. The residue is purified by using column chromatography on silica, yielding acetonide- fenoldopam 16.

10306] A mixture of acetonide- fenoldopam 16 (277 mg, 0.80 mmol), 2- Smethylpropene (67.0 mg, 1.20 mmol), and a catalytic amount of concentrated H 2 S0 4 in NO CH 2 C2 (20 mL) is stirred at room temperature overnight. The solution is washed with Ssaturated NaHCO 3 aqueous solution (2 times) and brine (2 times) and dried over 0O anhydrous MgSO 4 filtered and concentrated in vacuo. The residue is purified by using column chromatography on silica, yielding compound 17.

[03071 To a mixture of 17 (201 mg, 0.50 mmol) and N,N-diisopropylethylamine (129 mg, 1.0 mmol) in methylene chloride (20 mL) is added 4-iodobutyric acid (107 mg, 0.5 mmol). The resulting solution is stirred at room temperature overnight. The solution is washed with brine (2 times), dried over anhydrous MgSO 4 filtered and concentrated in vacuo. The residue is purified by using column chromatography on silica, yielding intermediate compound 18.

Example 11: Synthesis of intermediate compound (21) N N HN

H

O H OH H H 0 o H 19 20 21 103081 To a solution of 19 (169 mg, 1.0 mmol) in dioxane (20 mL) and water mL) is added 4-iodobutyric acid (214 mg, 1.0 mmol). The resulting solution is stirred for 24 hours. During this period of time, the pH of the solution is kept at 7-8 by adding N NaOH solution. The solvents are removed under reduced pressure. The residue is purified using column chromatography on silica, yielding compound [03091 To a solution of 20 (179 mg, 0.7 mmol) in dioxane (6 mL) and water (3 mL) is added IN NaOH (2.1 mL) at 0 OC. To the resulting solution is added di-tert-butyl dicarbonate (336 mg, 1.54 mmol) over the course of 30 minutes. The mixture is stirred at room temperature for 12 hours. Dioxane is removed under reduced pressure. To the H;\MaraR\Keep\Speci\P64463-div-SPECI.doc 7/02/08 00 64-

O

0 resulting water solution is added ethyl acetate. The pH of the solution is adjusted to Sabout pH 3 by the addition of 0.2 N HCI solution at 0 OC. The organic layer is Sseparated, washed with water (twice), dried over anhydrous MgSO 4 filtered and concentrated in vacuo. The residue is purified by using column chromatography on silica, yielding intermediate compound 21.

\O Example 12: Synthesis of intermediate compound (24) 0

OOH

00 OH H

N

0 10 O N H 1 N HN H \Q 0= 22 24 [03101 To a solution of 22 (169 mg, 1.0 mmol) in dioxane (20 mL) and water mL) is added 4-iodobutyric acid (214 mg, 1.0 mmol). The resulting solution is stirred for 24 hours. During this period of time, the pH of the solution is kept at 7-8 by adding N NaOH solution. The solvents are removed under reduced pressure. The residue is purified using column chromatography on silica, yielding compound 23.

[03111 To a solution of 23 (179 mg, 0.7 mmol) in dioxane (6 mL) and water (3 mL) is added IN NaOH (1.4 mL) at 0 OC. To the resulting solution is added di-tert-butyl dicarbonate (168 mg, 0.77 mmol) over the course of 30 minutes. The mixture is stirred at room temperature for 12 hours. The pH of the solution is adjusted to about 4-5 by addition of 0.2 N HC1 solution at 0 OC. The solution is concentrated in vacuo. The residue is purified by using column chromatography on silica, yielding intermediate compound 24.

Example 13: Synthesis of intermediate compound (27) 0- >H 0 HO H H H

OH

26 27 H:\MaraR\Keep\Speci\P64463-div-SPECIdoc 7/02/08 00 65 O0

O

[03121 A mixture of 25 (205 mg, 1.00 mmol), 2-methylpropene (84 mg, 1.50 mmol), j and concentrated H 2

SO

4 in CH 2 C12 (20 mL) is stirred at room temperature overnight.

The solution is washed with saturated NaHCO 3 in aqueous solution (2 times) and brine (2 times) and dried over anhydrous MgSO 4 filtered, and concentrated in vacuo. The residue is purified using column chromatography on silica, yielding compound 26.

NO [0313] To a mixture of 1-adamantanamine hydrochloride 26 (209 mg, 0.8 mmol) and SN,N-diisopropylethylamine (310 mg, 2.4 mmol) in methylene chloride (20 mL) is added oO 4-iodobutyric acid (171 mg, 0.8 mmol). The resulting solution is stirred at room O 10 temperature overnight. The solution is concentrated in vacuo. The residue is purified using column chromatography on silica, yielding intermediate compound 27.

Synthesis of other compounds 10314] The compounds listed below can be synthesized according to the procedures described above.

10315] For the introduction of Dopi, Dop2, Dop3 or Dop4 residue(s) into peptides, Dopl-OH, Dop2-OH, Dop3-OH or Dop4-OH (WO 02/100888 Al) was used during the syntheses, respectively.

[0316] For the synthesis of the Dop5 containing peptides, Fmoc-Dopa(acetonide)- OH (Novabiochem, San Diego, CA) was used.

[03171 For the Dop6 residue in peptides, compound 11 is used during the synthesis.

[0318] For the Dop7 residue in peptides, compound 21 is used during the synthesis.

[0319] For the Dop8 residue in peptides, compound 14 is used during the synthesis.

[0320] For the Dop9 residue in peptides, compound 24 is used during the synthesis.

[03211 For the Dopl0 residue in peptides, compound 3 is used during the synthesis.

[0322] For the Dopl 1 residue in peptides, compound 6 is used during the synthesis.

[0323] For the Dopl2 residue in peptides, compound 27 is used during the synthesis.

[0324] For the Dopl3 residue in peptides, compound 18 is used during the synthesis.

[03251 Table 1 lists somatostatin-dopamine chimeric analogs likely to have somatostatin and dopamine activity in vitro or in vivo.

Table 1 H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 7/02/08 00 66 Dop2-DPhe-Doc-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Ac-Lys(Dop2)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2 Ac-DLys(Dop2)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-Lys(Ac)-DTyr.-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DLys(Ac)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop3-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 IND Dop4-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 0o3Ap-~ecco[y-y-~pLsAuCs-h-H 00 Dop4-Aepa-DPhe-cyclollCys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2 0~0 Dop5-p-DPhe-cyc[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop6-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop7-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2 Dop7-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop8-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2 Dop 1 -DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 1 O-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dopl I2-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]l-Thr-NH 2 Dop 13 -DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 3Dh-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys-Thr-NH 2 Dop6-cyclo[Cys-Tyr-DTrp-Lys-Abu-CysI-Thr-NH 2 Dop6-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2 Dop8-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop9-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop I -cycoICys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 I 0-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop 1 I2-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dopl I -cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2 ID2-cyclo [Cys-Tyr-DTrp-Lys-aI-Cys] -Thr-NH 2 Dop6-D2NaI-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop7-D2Na1-cyclo[Cys-Tyr-DTrp-Lys-VaI-Cys]-Thr-NH2 30Dop8-D2Nal-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop9-D2Nal-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doC 7/02/08 00 67 Do0 -2a-y~~CsTr-~pLsV1Cs-h-H Dop 11 -D2Na1-cyclo[Cys-Tyr-DTrp-Lys-VaI-Cys]-Thr-NH 2 Dop 1 I2-D2Na1-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop 13 -D2NaI-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop5 -a-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop6-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH2 Dop7-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop8-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 00 Dop9-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop I -cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 11-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dopl 12-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dopl 13-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 -cyclo [Cys-P-DTrp-Lys-Tr-Cys]-Thr-oI2 15Dop6-DPhe-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol Dop7-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-oI Dop8-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol Dop9-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-oI Dop 1 -DPhe-cycoICys-Phe-DTrp-Lys-Thr-Cys]-Thr-o1 11-DPhe-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol Dop I I2-DPhe-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol Dop 13 -DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-oI I3Dh-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-oI Dop6-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol 25Dop7-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol 25Dop8-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-oI Dop9-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol Dop 1 -cyclo[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-oI Dop 11 -cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol I I2-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol Dop 13 -cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol [Cys-Tyr-DTrp-Lys-Thir-Cys]-2Nal-NH 2 H:\Maraf\Keep\Speci\P64463div-SPECI .doc 7/02/08 00 68 Dop6-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop7-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop8-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys]-2Na-NH 2 Dop9-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop I O-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop 11 -DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop 1 2-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2NaI-NH 2 Dop 1 3-DPhe-.cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2NaI-NH 2 00 Dop5-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2NaI-NH 2 Dop6-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop7-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2NaI-NH 2 Dop8-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2NaI-NH 2 Dop9-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop 1 0-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dopl 1-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2NaI-NH 2 Dopl12-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop13 -cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 DoplI-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dopl1-Aepa-DPhe-cyclolCys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop2-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop3 -Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop4-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop3 -DPhe-cyclo [Cys-3lTyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop4-DPhe-cyclo [Cys-3ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 -DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop6-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop7-DPhe-cyclo LCys-3ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop8-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop9-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop I O-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dopl 11-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECIdoc 7/02/08 00 69 Dop I 2-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop 1 3-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop3 -cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop4-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop5-cyclo[Cys-31ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop6-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop7-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop8-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 00 o9ccoCs3Iy-rpLsTrCs-h-H 10Dop9 -cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 I O-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dopl11-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop 1 -cyclo [Cys-3 lTyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dopl 13 -cyclo [Cys-3a-DTrp-Lys-rCys]-Thr()Tr-NH 2 Dop21-Caeg-cyclo [DCys-3 PalI-DTrp-Lys-DCys] -Thr(BzI)-Tyr-N H 2 15Dop2 -Caeg-cyclo [DCys-3 PalI-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-N H 2 Dop3 -Caeg-cyclo [DCys- 3 PalI-DTrp- Lys-DCys] -Thr(Bzl)-Tyr-N H 2 Dop4-p-Caeg-cyclo [DCys-3 Pa-DTrp-Lys-DCys]-Thr(Bzl)-Tyr-NH 2 Dop2I-Aepa-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys]-Tbr(Bzl)-Tyr-NH 2 20Dop2-Aepa-Caeg-cyclo [DCys-3 PaI-DTrp-Lys-DCys] -Thr(BzI)-Tyr-NH 2 20Dop3 -Aepa-Caeg-cyclo [DCys-3 PaI-DTrp-Lys-DCys] -Thr(BzI)-Tyr-NH 2 Dop4-p-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys]-Thr(BzI)-Tyr-NH2 [DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop6-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop7-Caeg-cyclo[DCys-3 Pal-DTrp-Lys-DCys]-Thr(Bzl)-Tyr-NH 2 25Dop8-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys]-Thr(Bzl)-Tyr-NH 2 Dop9-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop I IO-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(BzI)-Tyr-NH 2 Dopi I-Caeg-cyclo[DCys-3Pal-DTrp-Lys-DCys]-Thr(Bzl)-Tyr-NH2 30Dopl1 -Caeg-cyclo [DCys-3 PaI-DTrp-Lys-DCys] -Thr(BzI)-Tyr-NH 2 Dop 13-Caeg-cyclo [DCys-Pa-DTrp-Lys-DCys] -Tr(Bzl)-Tyr-NH 2 Dop21-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECT .doC 7/02/08 00 70 Dop3 -Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-NH 2 Dop4-Caeg-cyclo [DCys-Phe-DTrp- Lys- DCys] -Ser(Bz)-Tyr-NH2 Dop 1 -Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dop2-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dop3 -Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(13zl)-Tyr-NH 2 Dop4-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dop5-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bz)-Tyr-NH2 Dop6-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 00 Dop7-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dop8-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dop9-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bz)-Tyr-NH 2 Dop I O-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-NH 2 Dop I11 -Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dop 1 2-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 DopI 3-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-SerBzl)-Tyr-NH 2 [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]l-NH 2 Dop6-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH 2 Dop7-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop8-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop9-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop I 0-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop 1-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop I 2-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dopl 13-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop5-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop6-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop7-DPhe-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop8-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop9-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 DopI O-DPhe-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop 11I -DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop I 2-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECIdoC 7/02/08 00 71 Do Dop I3Dh-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH2 Dop6-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop7-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 5Dop8-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop9-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH2 Dop 1 -cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop I1 -cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH2 00 -yl[y-h-NM)Dr-y-h-y]Ti-H 00 Dop 1 2-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop 1 3-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH2 Dop2-Lys(Dop2)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-DLys(Dop2)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-Lys-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop I -Lys(Dop 1 )-DPhe-cyclo [Cys-Tyr-DTrp- Lys-Abu-Cys] -Thr-NH 2 Dop 1 -Lys(Dop I )-Aepa-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-N H 2 Dop 1 -Lys(DoplI)-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2 Dop I -Lys(DoplI)-Lys-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]l-Thr-NH2 Dop 1 -Lys(DoplI)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop I -DLys(Dop 1 )-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop I -DLys(Dop I )-Aepa-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop 1 -DLys(DoplI)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop I -DLys(Dop 1 )-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop I -DLys(Dop 1 )-DTyr-DTyr-cyclollCys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop I -Lys(DoplI)-D2NaI-cyclo[Cys-Tyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 Dop I -Lys(Dopl1)-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys]-Thr-NH 2 Dop I -Lys(Dopl1)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop 1 -Lys(Dopl1)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop 1 -Lys(Dopl1)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-N- 2 H\MaraR\Xeep\Speci\P64463-div-SPECI .doc 7/02/08 00 72 Dop I -Lys(DoplI)-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop I -Lys(DoplI)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop 1 -Lys(DoplI)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop I -Lys(DoplI)-DPhe-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol Dop 1 -Lys(DoplI)-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol Dop 1 -Lys(Dopl )-Lys-DTyr-DTyr-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-oI Dop I -Lys(DoplI)-DTyr-DTyr-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol Dop 1 -Lys(Dop2)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys]-Trp-NH 2 00 DoplI-Lys(Dop2)- cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 Dop I -Lys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 Dop 1 -Lys(Dop2)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Tmp-NH 2 Dop2-Lys(Dop2)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-Aepa-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]l-Thr-NH2 Dop2-Lys(Dop2)-Aepa-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-DLys(Dop2)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-Aepa-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-DLys(Dop2)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-Lys-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-Aepa-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-D2Na1-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-DPhe-cyclo [Cys-Tyr-DTrp.-Lys-Thr-Cys] -2Nal-NH 2 Dop2-Lys(Dop2)-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop2-Lys(Dop2)-Lys-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop2-Lys(Dop2)-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol Hi\maraR\Keep\speci\P64463-diV-SPECI .dOC 7/02/08 73 00 Do2LsDp)cco[y-heDr-y-h-y]Tro 0Dop2-Lys(Dop2)Ly-rDr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol N Dop2-Lys(Dop2)--DTyr-DTyr-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-o Dop2-Lys(Dop2)-D~yhe~y-cyclo[Cys--DTrp-Lys--Cys] -Trp-NH 5Dop2-Lys(Dop2)-D cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH 2 Dop2-Lys(Dop2)-Ly- -~rcyclo[Cys-Tyr-DTrp-Lys-VaI-Cys]-Trp-NH2 Dop2-Lys(Dop2)--DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 Dop3-Lys(Dop3)-D~yhe~y-cyclo [Cys-Tyr-DTrp-Lys-u-Cys] -Tr-NH 2 00 ~Dop3 -Lys(Dop3)-A-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 0 ~0 Dop3 -Lys(Dop3)-eaDh-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop3 -Lys(Dop3)-yDrDr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2 Dop3 -Lys(Dop3)--DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop3-Lys(Dop3 )-Dyhe~-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop3-DLys(Dop3 )-A-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 15Dop3-DLys(Dop3)-eDh-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop3 -DLys(Dop3)LyDrDr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys-Thr-NH 2 Dop3 -DLys(Dop3 )--DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop3 -Lys(Dop3 )-DNaI~y-cyclo[Cys-Tyr-DTrp-Lys-Ab-Cys] -Thr-NH 2 Dop3 -Lys(Dop3)-a-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys-Thr-NH 2 Dop3 -Lys(Dop3)Ly-rDy-cyclo [Cys-Tyr-DTrp-Lys- .VaI-Cys] -Thr-NH 2 Dop3 -Lys(Dop3)--DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop3 -Lys(Dop3)-D~yhe~y-cyclo [Cys-Tyr-DTrp-Lys--Cys] -a-NH 2 Dop3 -Lys(Dop3 )-D-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop3 -Lys(Dop3 )Ly-rDr-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH2 25Dop3 -Lys(Dop3)--DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Na-NH 2 Dop3 -Lys(Dop3)-D~yhe~y-cyclo [Cys-e-DTrp-Lys-Thr-Cys -r-lNH Dop3 -Lys(Dop3)-Dh-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-o Dop3 -Lys(Dop3 )Ly-rDr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-oI Dop3 -Lys(Dop3 )--DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-o 30Dop3 -Lys(Dop3 )-D~yhe~y-cyclo [Cys--DTrp-Lys--Cys] -Trp-NH Dop3-Lys(Dop3)-D cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 Dop3 -Lys(Dop3)-Ly- Dy-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Trp-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.dOC 7/02/08 00 74 Dop3 -Lys(Dop3)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 Dop4-Lys(Dop4)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-Lys(Dop4)-Aepa-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop4-Lys(Dop4)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-Lys(Dop4)-Lys-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-Lys(Dop4)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-DLys(Dop4)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-DLys(Dop4)-Aepa-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 00 Dop4-DLys(Dop4)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-N H 2 Dop4-DLys(Dop4)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-DLys(Dop4)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop4-Lys(Dop4)-D2Na1-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH2 Dop4-Lys(Dop4)-cyclo[Cys-Tyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 Dop4-Lys(Dop4)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Va-CysJ-Thr-NH 2 Dop4-Lys(Dop4)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop4-Lys(Dop4)-DPhe-cyclo [Cys-Tyr-DTrp- Lys-.Thr-Cys]-2Nal-NH 2 Dop4-Lys(Dop4)-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop4-Lys(Dop4)-Lys-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH2 Dop4-Lys(Dop4)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop4-Lys(Dop4)-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol Dop4-Lys(Dop4)-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol Dop4-Lys(Dop4)-Lys-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol Dop4-Lys(Dop4)-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-oI Dop4-Lys(Dop4)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 Dop4-Lys(Dop4)- cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Trp-NH 2 Dop4-Lys(Dop4)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys]-Trp-NH 2 Dop4-Lys(Dop4)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys]-Trp-NH 2 [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop5-Lys(Dop5)-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]1-Thr-NH 2 Dop5-Lys(Dop5)-Lys-DTyr-DTyr-cyclolCys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 -Thr-NH 2 [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 H:\MaraR\Xeep\Speci\P64463-div-SPECI .doc 7/02/08 00 [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 -Thr-NH 2 [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 -Lys(Dop5)-D2NaI-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop5 -Lys(Dop5)-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 DopS -Lys(Dop5)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 -Lys(Dop5)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 -Lys(Dop5)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 00 o5LsDp)ccoCsTrDr-y-h-y]2aNH Dop5 -Lys(Dop5)-yDrDr-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop5 -Lys(Dop5)--DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 [Cys-yr-DTrp-Lys-Thr-Cys]-2aINH [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-o -Lys(Dop5)-yDrDr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-o 15Dop5-Lys(Dop5)L-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-oI Dop5-Lys(Dop5)-D~yrDey-cyclo [C-ys--DTrp-Lys-hr-Cys] -Thr-ol cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 -~rcyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH 2 2 20Dop6-Lys(Dop5)-D~yrDe-cyclo[Cys-Tyr-DTrp-Lys-VI-Cys]-Tr-NH 2 Dop6-Lys(Dop6)-D-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop6-Lys(Dop6)-yDrDr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop6-Lys(Dop6)--DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop6-Lys(Dop6)-DyrDe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 25Dop6-DLys(Dop6)-D-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop6-DLys(Dop6)-yDrDr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop6-DLys(Dop6)--DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop6-Lys(Dop6)-DyrDay-cyclo[Cys-Tyr-DTrp-Lys-Ab-Cys] -Thr-NH 2 Dop6-Lys(Dop6)-2a-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop6-Lys(Dop6)-yDrDr-cyclo [Cys-Tyr-DTrp-Lys-Va -Cys] -Thr-NH 2 Dop6-Lys(Dop6)L-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Va-Cys]-Thr-NH 2 Dop6-Lys(Dop6)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 H:\MaraR\Kecp\Speci\P64463-div-SPECI.doc 7/02/08 00 76 Do6LsDp)cco[y-yrDr-y-h-y]2a-H Dop6-Lys(Dop6)LyDrDr-cyclo llCys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop6-Lys(Dop6)--DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH2 Dop6-Lys(Dop6)-D~yhe~y-cyclo[Cys- -DTrp-Lys-Thr-Cys] oI H 5Dop6-Lys(Dop6)-Dh-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-oI Dop6-Lys(Dop6)Ly-rDr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol Dop6-Lys(Dop6)--DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-oI Dop6-Lys(Dop6)-D~yhe~y-cyclo [Cys--DTrp-Lys--Cys] -Trp-NH 006LsDp)Dh-ccoCsTrDr-LsVlCs-r-H 00 Dop6-Lys(Dop6)- cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Tmp-NH 2 Dop6-Lys(Dop6)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys]-Trp-NH 2 Dop6-Lys(Dop6)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Tmp-NH 2 Dop7-Lys(Dop7)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop7-Lys(Dop7)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop7-DLys(Dop7)-DPhe-cyclolCys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop7-DLys(Dop7)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop7-Lys(Dop7)-D2Na1-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop7-Lys(Dop7)-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys]-Thr-NH 2 Dop7-Lys(Dop7)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop7-Lys(Dop7)-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop7-Lys(Dop7)-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol Dop7-Lys(Dop7)-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol Dop7-Lys(Dop7)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Tmp-NH 2 Dop7-Lys(Dop7)- cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Tmp-NH 2 Dop8-Lys(Dop8)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop8-Lys(Dop8)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop8-DLys(Dop8)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop8-DLys(Dop8)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop8-Lys(Dop8)-D2Na1-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop8-Lys(Dop8)-cyclo [Cys-Tyr-DTmp-Lys-Val-Cys] -Thr-NH 2 Dop8-Lys(Dop8)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop8-Lys(Dop8)-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2NaI-NH 2 Dop8-Lys(Dop8)-DPhe-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-oI HL\MaraR\Keep\Speci\P64463-div-SPECIdoc 7/02/08 00 77 Dop8-Lys(Dop8)-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-oI Dop8-Lys(Dop8)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH 2 Dop8-Lys(Dop8)- cyclo[Cys-Tyr-DTrp-Lys-VaI-Cys] -Trp-NH 2 Dop9-Lys(Dop9)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop9-Lys(Dop9)-cyclollCys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop9-DLys(Dop9)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 No Dop9-DLys(Dop9)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop9-Lys(Dop9)-D2NaI-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 00 Dp-y(o9-yl[y-y-~pLsVlCs-h-H Dop9-Lys(Dop9)-Dh-cyclo [Cys-Tyr-DTrp-Lys--Cys]- -NH 2 Dop9-Lys(Dop9)-D-cyclolCys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop9-Lys(Dop9)-Dh-cyclo[Cys--DTrp-Lys-Thr-Cys] 2Nal-NH Dop9-Lys(Dop9)-Dcyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol Dop9-Lys(Dop9)-cyhcl[ys-Phesy-DTrp-Lys--Cys] -Thr-ol 15Dop9-Lys(Dop9)-D cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 15Dop9-Lys(Dop)-D ycl o[Cys-Tyr-DTrp-Lys-Cs]-rp-hr-H Dop I -Lys(DoplI )-Dh-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop I O-DLys(Dop I 0)-Dh-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys-Thr-NH 2 Dop 1 O-DLys(Dop 1 0)-Dh-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop 1 0-Lys(Dop 1 )D2-cyclo[Cys-Tyr-DTrp-Lys-u-Cys] -Thr-NH 2 Dop 1 O-Lys(Dop 1 0)Da-cyclo [Cys-Tyr-DTrp-Lys-.Val-Cys]-Thr-NH 2 Dop 1 0-Lys(Dop I 0)-Dh-cyclo [Cys-Tyr-DTrp-Lys--Cys]-l-NH 2 Dopl 1 -Lys(Dop 1 0)-Dh-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dopl I -Lys(Dop I 0)-Dh-cyclo[Cys--DTrp-Lys-Thr-Cys] 2Na1-NH 1 -Lys(Dop 1 0)-Dh-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol I -Lys(Dop 1 0)-cyhcl cys-Phey-DTrp-Lys--Cys] -Thr Dop I -Lys(DoplI cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Trp-NH 2 Dopi 0-Lys(DopIOl)-D cyclo[Cys-Tyr-DTrp-Lys-A-Cys]-T -NH2 Dopl 11-Lys(Dop 11)-Dh-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop I11 -Lys(Dop I )-D-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop I I -DLys(Dop I 1 )-D-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop I-Lys(Dop I)2a-cyclo[Cys-Tyr-DTrp-Lys-u-Cys]-Thr-NH 2 H'\MaraR\Keep\SpeCi\P64463-div-SPECI .doc 7/02/08 00 78 Dopl 11-Lys(Dopl 11)-cyclo[Cys-Tyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 Dop I11 -Lys(Dop 11 )-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Na-NH 2 Dopl 11-Lys(Dopl 11)-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop 11 -Lys(Dopl 11)-DPhe-cyclo (Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol Dopl 11-Lys(Dopl 11)-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol Dopi 1-Lys(Dopl 1)-DPhe-cycloljCys-Tyr-DTrp-Lys-VaI-Cys]-Trp-NH 2 No Dop II-Lys(Dopl 1 cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH2 Dop 1 2-Lys(Dop I 2)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 00 Dp2LsDp2-yl[y-y-~pLsAuCs-h-H 10Dopl12-DLys(Dopl2)-Dh-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] Tin-NH 2 Dop I 2-DLys(Dop 1 2)-Dh-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys-Thr-NH 2 Dop 1 2-Lys(Dop 1 2)2a-cyclo[Cys-Tyr-DTrp-Lys-u-Cys]-Thr-NH 2 Dop 1 2-Lys(Dop I 2)D2a-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop I 2-Lys(Dop I 2)-Dh-cyclo [Cys-Tyr-DTrp-Lys--Cys]-l-NH 2 I 2-Lys(Dop I 2)-Dh-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 I 2-Lys(Dop I 2)-Dh-cycloCys--DTrp-Lys-Thr-Cys]-l- Dop I 2-Lys(Dop I 2)-Dh-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-oI Dop 1 2-Lys(Dop I 2)-cyhcl Che-DTrp-Lys--Cys] -Tr DoplI2-Lys(DoplI2)-D cyclo[Cys-Tyr-DTrp-Lys-Val-Cysl-Trp-NH 2 Dopl1 -Lys(Dop 12)-D cyclo [Cys-Tyr-DTrp-Lys-A-Cys]- -NH 2 DoplI3-Lys(DoplI3)-Dh-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2 Dop 13 -Lys(Dopl )-Dh-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dopl13-DLys(DoplI )-Dh-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -in-NH 2 Dop 13-Lys(DopI3)2a-cyclo [Cys-Tyr-DTrp-Lys-u-Cys] -T-NH 2 Dop13 -Lys(Dopl13)-a-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 25Dop13 -Lys(DoplI3)-Dh-cyclo[Cys-Tyr-DTrp-Lys--Cys]--NH 2 Dop13 -Lys(Dopl13)-Dh-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop13 -Lys(DoplI3)-Dh-cyclo [Cys--DTrp-Lys-Thr-Cys] 2Nal-NH Dop13 -Lys(DoplI3)-Dh-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-oI Dop13 -Lys(Dopl13)-Dh-cyclo[Cys- -DTrp-Lys--Cys]-Tr H Dop13 -Lys(Dopl13)-D cyclolCys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH 2 Dop I -Lys(DoplI)-Caeg-cyc lo [DCys-3 Pal-DTrp- Lys- DCys] -Thr(Bzl)-Tyr-NH2 H:\MaraR\Keep\Speci\P64463-div-SPECI .doc ?/02/08 00 79 0 Dop I -Lys(Dop 1 )-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bz)-Tyr-NH 2 Dop I -DLys(Dopl1)-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop 1 -DLys(Dop I )-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dop 1 -Lys(Dop I )-Lys-Caeg-cyclo[DCys-3 Pal-DTrp-Lys-DCys] -Thr(BzI)-Tyr-NH 2 Dop I -Lys(DoplI)-Lys-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dop 1 -DLys(Dop 1 )-Lys-Caeg-cyclo[DCys-3 PaI-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop I -DLys(DoplI)-Lys-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr-NH 2 Dop 1 -Lys(Dop I )-Aepa-Caeg-cyclo [DCys-3 PalI-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-N H 2 00 Dop I -Lys(Dop 1 )-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dop I -DLys(Dop 1 )-Aepa-Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(Bzl)-Tyr-N H 2 Dop 1 -DLys(Dop 1 )-Aepa-Caeg-cyclollDCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-NH2 Dop 1 -Lys(Dop 1I)- Lys-Aepa-Caeg-cyclo [DCys-3 Pal -DTrp- Lys-DCys] -Thr(Bzl)-Tyr-

NH

2 Dop I -Lys(DoplI)-Lys-Aepa-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-

NH

2 Dop I -DLys(Dop 1 )-Lys-Aepa-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(BzI)-Tyr- NH4 2 Dop I -DLys(Dop I )-Lys-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-

NH

2 Dop2-Lys(Dop2)-Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DC ys] -Thr(Bzl)-Tyr-NH 2 Dop2-Lys(Dop2)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr-NH 2 Dop2-DLys(Dop2)-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop2-DLys(Dop2)-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bz)-Tyr-NH2 Dop2-Lys(Dop2)-Lys-Caeg-cyclo [DCys-3 PaI-DTrp-Lys-DCys] -Thr(Bz1)-Tyr-NH 2 Dop2-Lys(Dop2)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dop2-DLys(Dop2)- Lys-Caeg-cyclo [DCys-3 Pal- DTrp- Lys-DCys] -Thr(Bz)-Tyr-N H 2 Dop2-DLys(Dop2)-Lys-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bz)-Tyr-NH2 Dop2-Lys(Dop2)-Aepa-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys]-Thr(Bz)-Tyr-NH 2 Dop2-Lys(Dop2)-Aepa-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dop2-DLys(Dop2)-Aepa-Caeg-cyclo[DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop2-DLys(Dop2)-Aepa-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI .doc 7/02/08 00 80 Dop2-Lys(Dop2)-Lys-Aepa-Caeg-cyclo [DCys-3 PaI-DTrp-Lys-DCys]-Thr(Bzl)-Tyr- NH1 2 Dop2-Lys(Dop2)-Lys-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr- NH1 2 Dop2-DLys(Dop2)-Lys-Aepa-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-

NH

2 Dop2-DLys(Dop2)-Lys-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr- NH1 2 00 Dop3 -Lys(Dop3)-Caeg-cyclo[DCys-3Pal-DTrp-Lys-DCys] -Thr(BzI)-Tyr-NH 2 Dop3 -Lys(Dop3)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dop3 Lys(Dop3 )-Lys-Caeg-cyclo [DCys-3 Pal -DTrp- Lys-DCys] -Thr(BzI)-Tyr-NH 2 Dop3 -Lys(Dop3 )-Lys-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr-NH 2 Dop3 -Lys(Dop3 )-Aepa-Caeg-cyclo [DCys-3Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop3 -Lys(Dop3)-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr-NH 2 Dop3 -DLys(Dop3 )-Caeg-cyclo[DCys-3 PaI-DTrp-Lys-DCys]-Thr(BzI)-Tyr-NH 2 Dop3 -DLys(Dop3 )-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bz)-Tyr-NH 2 Dop3 -DLys(Dop3 )-Lys-Caeg-cyclo [DCys-3 PaI-DTrp-Lys-DCys]-Thr(Bzl)-Tyr-NH 2 Dop3 -DLys(Dop3 )-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-NH2 Dop3 -DLys(Dop3 )-Aepa-Caeg-cyclolDCys-3 Pal-DTrp-Lys-DCysl-Thr(Bzl)-Tyr-NH 2 Dop3 -DLys(Dop3 )-Aepa-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(3z)-Tyr-NH2 Dop4-Lys(Dop4)-Caeg-cyclo[DCys-3 Pal-DTrp-Lys-DCys]-Thr(Bzl)-Tyr-NH 2 Dop4-Lys(Dop4)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(BzI)-Tyr-NH 2 Dop4-Lys(Dop4)-Lys-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(BzI)-Tyr-NH 2 Dop4-Lys(Dop4)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-NH 2 Dop4-Lys(Dop4)-Aepa-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop4-Lys(Dop4)-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-NH 2 Dop4-Lys(Dop4)-Lys-Aepa-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr- NH1 2 Dop4-Lys(Dop4)-Lys-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr- NH1 2 Dop4-DLys(Dop4)-Caeg-cyclo [DCys-3 Pal- DTrp-Lys- DCys] -Thr(BzI)-Tyr-NH 2 Dop4-DLys(Dop4)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doC 7/02/08 00 81 Dop4-DLys(Dop4)-Lys-Caeg-cyclo[DCys-3 PalI-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop4-DLys(Dop4)-Lys-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dop4-DLys(Dop4)-Aepa-Caeg-cyclo [DCys-3 PaI-DTrp-Lys-DCys] -Thr(BzI)-Tyr-NH 2 Dop4-DLys(Dop4)-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dop4-D Lys(Dop4)- Lys-Aepa-Caeg-cyclo [DCys-3 PalI-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-

NH

2 Dop4-DLys(Dop4)-Lys-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-

NH

2 00 o5LsDp)Ce-yl[ys3aDrpLsDy]TrBlTy-H Dop5-Lys(Dop5)-Caeg-cyclo[DCys-3Pa-DTrp-Lys-DCys]-Thr(Bzl)-Tyr-NH 2 10Dop5-Lys(Dop5)-Caeg-cyclo[DCys-P-DTrp-Lys-DCys]-er(Bzl)-Tyr-NH2 -DLys(Dop5)-Caeg-cyclo [DCys-3Pa-DTrp-Lys-DCys] -Tr(Bzl)-Tyr-NH 2 -er(Bzl)-Tyr-NH 2 Dop5-Lys(Dop5)-Lys-Caeg-cyclo[DCys-3Pal-DTrp-Lys-DCys]-Thr(Bzl)-Tyr-NH2 Dop5 -Lys(Dop5)-Lys-Caeg-cycl o[DCys-Pl-DTrp-Lys-DCys] -er(Bzl)-Tyr-N H2 Dop5-DLys(Dop5)-Lys-Caeg-cyclo[DCys-3Pa-DTrp-Lys-DCys] -Tr(Bz)-Tyr-NH 2 )y-Caeg-cyclo[DCys-Pe-DTrp-Lys-DCys]-er(BzI)-Tyr-NH2 Dop6-Lys(Dop6)-Caeg-cyclo [DCys-3Pa-DTrp-Lys-DCys] -Tr(Bzl)-Tyr-NH 2 Dop6-Lys(Dop6)-Caeg-cyco DCys-Pl-DTrp-Lys- DCys] -r(Bz)-Tyr-NH2 20Dop6-DLys(Dop6)-Caeg-cyclo[DCys-3Pa-DTrp-Lys-DCys] -Tr(Bzl)-Tyr-NH 2 20Dop6-Lys(Dop6) -Caeg-cycl o [DCys-Pl-DTrp-Lys-DCys] -er(Bzl)-Tyr-NH 2 Dop6-Lys(Dop6)-Lys-Caeg-cyclolDCys-3Pa-DTrp-Lys-DCys] -Tr(Bz)-Tyr-NH 2 Dop6-Lys(Dop6)-Lys-Caeg-cyclo[DCys-Pe-DTrp-Lys-DCys] -er(Bzl)-Tyr-NH 2 Dop6-DLys(Dop6)-Lys-Caeg-cyclo[DCys-3Pa-DTrp-Lys-DCys] -Tr(Bzl)-Tyr-NH 2 25Dop6-Lys(Dop)--Caeg-cyclo[DCys-Pe-DTrp-Lys-DCys] -r(BzI)-Tyr-NH 2 Dop7-Lys(Dop7)-Caeg-cyclo[DCys-3Pal-DTrp-Lys-DCys]-Thr(Bzl)-Tyr-NH2 Dop7-Lys(Dop7)--Caeg-cyclo [DCys-Pl-DTrp-Lys-DCys] -r(Bzl)-Tyr-NH 2 Dop7-Lys(Dop7)-Lys-Caeg-cyclo[DCys-3Pa-DTrp-Lys-DCys] -Tr(Bzl)-Tyr-NH 2 Dop7-Lys(Dop7)-LCaeg-.cyclo[DCys-Pe-DTrp-Lys-DCys] -er(BzI)-Tyr-NH 2 Dop8-Lys(Dop8)-Caeg-cyclo[DCys-3Pa-DTrp-Lys-DCys]-Thr(Bzl)-Tyr-NH 2 30Dop8-Lys(Dop8)--Caeg-cyclo [DCys-P-DTrp-Lys-DCys]-r(Bzl)-Tyr-NH 2 Dop8-Lys(Dop8)-Lys-Caeg-cyclo [DCys-3Pa-DTrp-Lys-DCys] -Tr(Bzl)-Tyr-NH 2 H:\MaraR\Keep\Speci\P64463divSPECI.doc 7/02/08 00 82 Do9LsDp)Ce-yl[0s3PlDr-y-~s TrBI-y-H Dop9-Lys(Dop9)-Caeg-cyclo [DCys-3Pe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dop9-Lys(Dop9)L-Caeg-cyclo [DCys-PI-DTrp-Lys-DCys] -hr(Bzl)-Tyr-NH 2 Dop9-Lys(Dop9)- Lys-Caeg-cyclo [DCys-3Pale-DTrp-Lys-DCys] -er(Bz)-Tyr-N H 2 Dop 1 -Lys(Dop9)-LO)-Caeg-cyclo [DCys-PaI-DTrp-Lys-DCys]-hr(Bz)-Tyr-NH 2 Dop 1 O-Lys(Dop I 0)-Caeg-cyclo [DCys-3Pale-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-N H 2 Dop I O-Lys(Dop 1 0)L-Caeg-cyclo[DCys-P l-DTrp-Lys-DCys]-hr(Bzl)-Tyr-NH 2 Dop 1 O-Lys(Dop I 0)-Lys-Caeg-cyclo[DCys-3Pe-DTrp-Lys-DCys] -Ser(Bz)-Tyr-NH 2 00 Dop 11 -Lys(Dop 11)L-Caeg-cyclo [DCys-P-DTrp-Lys-DCys] -hr(Bz)-Tyr-NH 2 00~1 Dop I 1 -Lys(Dopl I )-Caeg-cyclo [DCys-3Pa- DTrp-Lys-DCys] -er(Bzl)-Tyr-N H 2 I -Lys(DopI 1 )L-Caeg-cyclo[DCys-PI-DTrp-Lys-DCys]-hr(BzI)-Tyr-NH 2 DopI 11-Lys(Dopl 11)-Lys-Caeg-cyclo [DCys-Pale-DTrp-Lys-DCys] -er(Bz)-Tyr-NH 2 Dopl 1 -Lys(Dopl 1 )--Caeg-cyclo[DCys-P-DTrp-Lys-DCys] -hi(Bz)-Tyr-NH 2 Dop 1 2-Lys(Dop I 2)-Caeg-cyclo [DCys-3Pal -DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 DoplI2-Lys(Dopl12)L-Caeg-cyclo [DCys-P l-DTrp-Lys-DCys] -hr(Bzl)-Tyr-NH 2 2-Lys(Dopl 2)-Lys-Caeg-cyclo[DCys-3Pe-DTrp-Lys-DCys]-er(Bz)-Tyr-NH2 Dopl13-Lys(Dopl13)--Caeg-cyclo [DCys-P-DTrp-Lys-DCys]-r(Bzl)-Tyr-NH 2 Dopi 3-Lys(DopI 3)-Caeg-cyclo[DCys-3Pe-DTrp-Lys-DCys]-er(Bz)-Tyr-NH 2 DoplI3-Lys(DoplI3)L-Caeg-cyclo[DCys-PI-DTrp-Lys-DCys]-hr(Bzl)-Tyr-NH2 13 -Lys(Dop I 3)-Lys-Caeg-cyclo [DCys-3Pal- DTrp- Lys-DCys] -Ser(Bzl)-Tyr-N H 2 Dopl1-Lys(DoplI)-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dopl1-Lys(DoplI)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 DoplI-DLys(DoplI)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dopl1-DLys(Dopl1)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dopl1-Lys(Dopl1)-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dopl1-DLys(Dopl1)-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop2-Lys(Dop2)-DPhe-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop2-DLys(Dop2)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH 2 Dop2-DLys(Dop2)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop2-DLys(Dop2)-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 H:\PMaraR\Keep\Speci\P64463-div-SPECI.doc 7/02/08 00 83 Do30y(o3-yl CsPePeDr-y-h-h-y]-H Dop3 -Lys(Dop3 )-D-cyclo[Cys-Phe-N-DTrp-Lys-Thr -Cys] h-NH 2 Dop3 -Lys(Dop3)-Dh-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop4-Lys(Dop4)-cyclo [Cys-Phe-Ph-eDTrp-Lys-Thrh-Cys]--NH 2 Dop4-Lys(Dop4)-D-cyclo [Cys-Phe-N-DTrp-Lys-Thr -Cys] h-NH 2 Dop4-Lys(Dop4)-Dh-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH2 2 [Cys-Phe-N-DTrp-Lys-Thr -Cys]h-NH 2 005LsDp)Dh-ycoCsPe(-eDrpLsTrCs-h-H 00Dop5 -DLys(Dop5 )-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop5-DLys(Dop5)-DPhe-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH2 [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop6-Lys(Dop6)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH 2 Dop6-Lys(Dop6)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop6-DLys(Dop6)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH 2 Dop6-DLys(Dop6)-DPhe-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH2 Dop6-Lys(Dop6)-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop6-DLys(Dop6)-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop7-Lys(Dop7)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH2 Dop7-Lys(Dop7)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH2 Dop7-Lys(Dop7)-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH2 Dop8-Lys(Dop8)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop8-Lys(Dop8)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop9-Lys(Dop9)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop9-Lys(Dop9)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop 1 O-Lys(Dopl 1 )-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop I O-Lys(Dopl 1 )-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dopl I-Lys(Dop I I)-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop I11 -Lys(Dopl Ii)-DPhe-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH2 Dopl12-Lys(DopI 2)-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 DoplI2-Lys(Dopl12)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 DoplI3-Lys(DoplI3)-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-N1 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doC 7/02/08 00 84 Dopl 13-Lys(Dop I 3)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop I -DPhe-cyclo [Cys-3 ITyr(Dopl1)-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop 1 -DPhe-Doc-DPhe-cyclo [Cys-3 ITyr(DoplI)-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop I -DLys(Dopl1)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop I -DLys(Dopl1)-Aepa-DPhe-cyclo[Cys-31ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop 1 -Lys(Dopl1)-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop I -Lys(Dopl1)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop 1 -Lys(DoplI)-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 00 Dop 1 -DLys(Dop 1 )-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop 1 -Lys(DoplI)-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop 1 -Lys(Dopl1)-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop I -DLys(Dopl1)-DTyr-DTyr-cyclo [Cys-31ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop 1 -DLys(Dopl1)-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop I -DLys(DoplI)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop1 -DLys(Dop l)-Aepa-DPhe-cyclo[lCys-31Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2 Dop I -Lys(DoplI)-DTyr-DTyr-cyclo [Cys-31ITyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop 1 -Lys(Dopl1)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop 1 -Lys(DoplI)-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop I -DLys(Dopl1)-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop 1 -Lys(DoplI)-cyclo[Cys-31ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop I -Lys(DoplI)-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop I -DLys(Dopl1)-DTyr-DTyr-cyclo [Cys-31ITyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop 1 -DLys(Dopl1)-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop 1 -DLys(Dopl1)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop I -DLys(DoplI)-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-VaI-Cys]-Thr-NH 2 Dop 1 -Lys(Dopl1)-DTyr-DTyr-cyclo[Cys-31ITyr-DTrp-Lys-Val-Cys] -Thr-N H 2 Dop I -Lys(Dopl1)-DPhe-cyclo [Cys-31ITyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop I -Lys(Dopl1)-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop I -DLys(Dopl1)-cyclo [Cys-3 ITyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 Dop I -Lys(DoplI)-cyclo[Cys-31ITyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop I -Lys(DoplI)-Lys-DTyr-DTyr-cyclo [Cys-31ITyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dopl -DLys(Dopl )-DTyr-DTyr-cyclo[Cys-3ITyr-DTrp-Lys-Va-CysI-Thr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI-doc 7/02/08 00 85 Dop 1 -DLys(Dop l )-Lys-DTyr-DTyr-cyclo [Cys-31ITyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop2-DPhe-cyclo [Cys-3 ITyr(Dop2)-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclolCys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-Aepa-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys.-Thr-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop2-DLys(Dop2)-DPhe-cyclo [Cys-3 lTyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Example 1 Dop2-DLys(Dop2)-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 00 Dop2-DLys(Dop2)-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop2-DLys(Dop2)-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-Aepa-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop2-DLys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-DLys(Dop2)-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-Aepa-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-DTyr-DTyr-cyclolCys-3 ITyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-DLys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Vat-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr-NH2 Dop2-Lys(Dop2)-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-cyclo [Cys-3 ITyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-Lys-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-Val-Cys] -Thr-NH 2 HA\MaraR\Keep\Speci\P64463-div-SPECI.doc 7/02/08 00 86 Dop2-DLys(Dop2)-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop2-DLys(Dop2)-Lys-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop3 -Lys(Dop3 )-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop4-Lys(Dop4)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop3 -Lys(Dop3)-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop4-Lys(Dop4)-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 -DLys(Dop5)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop5-Lys(Dop5)-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 00 o5LsDp)Dh-yl[y3ly-rpLsTrCsTh-H 10Dop5 -Lys(Dop5)D-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 10Dop5-Lys(Dop5 )-cyclo [Cys-3 Tyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 -Lys(Dop5)-yDrDr-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 [Cys-3 Tyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop5-DLys(Dop5)--DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop5-DLys(Dop5)L-D~yrey-cyclo [Cys-3 ITyr-DTrp-Lys- Thr-Cys]-Thr-NH 2 15Dop5 -Lys(Dop5)-Dyhe~-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop5-Lys(Dop5)-D~yrDey-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 -Lys(Dop5)D-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 -Lys(Dop5 )-cyclo [Cys-3 Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 DopS -Lys(Dop5)-yDrDr-cyclo [Cys-3 Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop5-Lys(Dop5)Ly-DTyr-DTyr-cyclo[Cys-3 Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 -DLys(Dop5 )--DTyr-DTyr-cyclo [Cys-3 Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 -DLys(Dop5)--D~yrey-cyclo [Cys-3 ITyr-DTrp-Lys- Abu-Cys] -Thr-NH 2 )-Dyhe.-cyclo [Cys-3 Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 25Dop5-Lys(Dop5)-D~yrDey-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys] -Thr-N 2 Dop5 -Lys(Dop5)D-cyclo[Cys-3 Tyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 [Cys-3 ITyr-DTrp-Lys-Va-Cys]-Thr-NH 2 Dop5-Lys(Dop5)-yDrDr-cyclo[Cys-3 Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 [Cys-3 Tyr-DTrp-Lys-Va-Cys] -Thr-NH 2 Dop5-DLys(Dop5 )--DTyr-DTyr-cyclo[Cys-3lTyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop5-Lys(Dop)LyDyrDr-cyclo [Cys-3 ITyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 Dop6-Lys(Dop6)-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thir-NH 2 H:\MaraR\KeeP\Speci\P64463-div-SPECIdoc 7/02/08 00 87 00 Dop8-Lys(Dop8)-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop9-Lys(Dop9)-cycloCys-3Tyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 DopI O-Lys(Dop I 0)-cyclo[Cys-3Tyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop 11-Lys(Dopl1 )-cyclo[Cys-3ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop l2-Lys(Dopl2)-cyclo[Cys-3ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 SDop 13-Lys(Dop 13)-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop6-Lys(Dop6)-DPhe-cyclo[Cys-3 Tyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 O Dop7-Lys(Dop7)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 00 Dop8-Lys(Dop8)-DPhe-cyclo[Cys-3ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop9-Lys(Dop9)-DPhe-cyclo[Cys-3ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop 10O-Lys(Dop 1 O)-DPhe-cyclo[Cys-3ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop I-Lys(Dop ll)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop 12-Lys(Dopl2)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop 13-Lys(Dopl3)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 [03261 Some of the compounds of the instant invention have at least one asymmetric center. Additional asymmetric centers may be present in the molecule depending upon the nature of the various substituents of the molecule. Each such asymmetric center will produce two optical isomers and it is intended that all such optical isomers, as separated, pure or partially purified optical isomers, racemic mixtures or diastereomeric mixtures thereof, are included within the scope of the instant invention.

[0327] The compounds of the instant invention generally can be provided in the form of their pharmaceutically acceptable acid addition salts, such as the salts derived from using inorganic and organic acids. Examples of such acids are hydrochloric, nitric, sulfuric, phosphoric, formic, acetic, trifluoroacetic, propionic, maleic, succinic, D-tartaric, L-tartaric, malonic, methane sulfonic and the like. In addition, certain compounds containing an acidic function such as a carboxy can be isolated in the form of their inorganic salt in which the counter-ion can be selected from sodium, potassium, lithium, calcium, magnesium and the like, as well as from organic bases.

[0328] The pharmaceutically acceptable salts can be formed by taking about 1 equivalent of a compound of the invention and contacting it with about I equivalent or H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 7/02/08 00 88 00 more of the appropriate corresponding acid of the salt which is desired. Work-up and isolation of the resulting salt is well-known to those of ordinary skill in the art.

103291 The compounds of this invention can be administered by oral, parenteral intramuscular, intraperitoneal, intravenous or subcutaneous injection, or implant), nasal, vaginal, rectal, sublingual or topical routes of administration and can be formulated with pharmaceutically acceptable carriers to provide dosage forms NO appropriate for each route of administration. Accordingly, the present invention features pharmaceutical compositions comprising, as an active ingredient, at least one 00 compound of the invention in association with a pharmaceutically acceptable carrier.

O 10 103301 Solid dosage forms for oral administration include capsules, tablets, pills, powders and granules. In such solid dosage forms, the active compound is admixed with at least one inert pharmaceutically acceptable carrier such as sucrose, lactose, or starch. Such dosage forms can also comprise, as is normal practice, additional substances other than such inert diluents, lubricating agents such as magnesium stearate. In the case of capsules, tablets and pills, the dosage forms may also comprise buffering agents. Tablets and pills can additionally be prepared with enteric coatings.

[0331] Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, the elixirs containing inert diluents commonly used in the art, such as water. Besides such inert diluents, compositions can also include adjuvants, such as wetting agents, emulsifying and suspending agents, and sweetening, flavoring and perfuming agents.

103321 Preparations according to this invention for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions, or emulsions. Examples of nonaqueous solvents or vehicles are propylene glycol, polyethylene glycol, vegetable oils, such as olive oil and corn oil, gelatin, and injectable organic esters such as ethyl oleate.

Such dosage forms may also contain adjuvants such as preserving, wetting, emulsifying, and dispersing agents. They may be sterilized by, for example, filtration through a bacteria-retaining filter, by incorporating sterilizing agents into the compositions, by irradiating the compositions, or by heating the compositions. They can also be manufactured in the form of sterile solid compositions which can be dissolved in sterile water, or some other sterile injectable medium immediately before use.

H;\MaaR\Keep\Speci\P6443-div-SPECI doc 7/02/08 00 89

O

0 [0333] Compositions for rectal or vaginal administration are preferably suppositories which may contain, in addition to the active substance, excipients such as coca butter or Sa suppository wax.

[0334] Compositions for nasal or sublingual administration are also prepared with standard excipients well known in the art.

[03351 In general, an effective dose of an active ingredient in the compositions of \C this invention may be varied; however, it is necessary that the amount of the active Singredient be such that a suitable dosage form is obtained. The selected dosage depends 00 upon the desired therapeutic effect, on the route of administration, and on the duration of the treatment, all of which are within the realm of knowledge of one of ordinary skill in the art. Generally, dosage levels of between 0.0001 to 100 mg/kg of body weight daily are administered to humans and other animals, mammals.

[0336] Preferred dosage ranges are from 0.01 to 10.0 mg/kg of body weight. Such dosages may be administered, for example, daily as a single dose or divided into multiple doses.

Somatostatin Receptor Specificity and Selectivity Assay 10337] Specificity and selectivity of the somatostatin analogues used to synthesize the somatostatin-dopamine chimers was determined by a radioligand binding assay on CHO-K1 cells stably transfected with each of the SSTR subtypes, as follows.

Somatostatin analogs are also described in U.S. Patent Application Publication No.

02210006790. The complete coding sequences of genomic fragments of the SSTR 1 Genbank accession No. M81829), SSTR 2 Genbank accession No.

M81830), SSTR 3 Genbank accession No. L07062), and SSTR 4 Genbank accession No. AL049651) genes and a cDNA clone for SSTR 5 Genbank accession No. D16827) was subcloned into the mammalian expression vector pCMV (Life Technologies, Milano, Italy). Other SSTR sequences are known to the skilled artisan. Clonal cell lines stably expressing SSTR's 1-5 were obtained by transfection into CHO-K1 cells (ATCC, Manassas, Va, USA) using the calcium phosphate coprecipitation method (Davis L, et al., 1994 In: Basic methods in Molecular Biology, 2nd edition, Appleton Lange, Norwalk, CT, USA: 611-646). The plasmid pRSV-neo (ATCC) was included as a selectable marker. Clonal cell lines were selected in RPMI H:\MaraR\Keep\Speci\P64463-div-SPECIdoc 7/02/08 90 00 01640 media containing 0.5 mg/ml of G418 (Life Technologies, Milano, Italy), ring cloned, and expanded into culture.

S[0338] Membranes for in vitro receptor binding assays were obtained by homogenizing the CHO-K1 cells expressing the SSTR's subtypes in ice-cold 50 mM Tris-HCI and centrifuging twice at 39000 g (10 min), with an intermediate resuspension Sin fresh buffer. The final pellets were resuspended in 10 mM Tris-HCl for assay.

0339] For the SSTR 1, 3, 4, and 5 assays, aliquots of the membrane preparations Swere incubated 90 minutes at 25 0 C with 0.05 nM 25 I-Tyrl 1]SS-14 in 50 mM HEPES 00 (pH 7.4) containing 10 mg/ml bovine serum albumin (BSA), 5 mM MgCI 2 200 KIU/ml 0 10 Trasylol, 0.02 mg/ml bacitracin, and 0.02 mg/ml phenylmethylsuphonyl fluoride. The final assay volume was 0.3 ml.

[0340] For the SSTR 2 assay, 0.05 nM [125I]MK-678 was employed as the radioligand and the incubation time was 90 minutes at 25 The incubations were terminated by rapid filtration through GF/C glass microfibre filters (Whatman Co.) (presoaked in 0.3% polyethylenimine) using a BRANDEL filtration manifold. Each tube and filter was washed three times with 5 ml aliquots of ice-cold buffer. Specific binding was defined as the total radioligand bound minus that bound in the presence of 1000 nM SS-14 for SSTR 1, 3, 4, and 5, or 1000 nM MK-678 for SSTR2.

Dopamine Receptor Specificity and Selectivity Assay [0341] Specificity and selectivity for the dopamine-2 receptor of the dopamine analogues used to synthesize the somatostatin-dopamine chimers may be determined by a radioligand binding assay as follows.

[0342] Crude membranes were prepared by homogenization of frozen rat corpus striatum (Zivic Laboratories, Pittsburgh, PA) in 20 ml of ice-cold 50 mM Tris-HCl with a BRINKMAN POLYTRON cell disrupter (setting 6, 15 sec). Buffer was added to obtain a final volume of 40 ml, and the homogenate was centrifuged in a SORVAL SS- 34 rotor at 39,000 g for 10 minutes at 0-4 The resulting supernatant was decanted and discarded. The pellet was rehomogenized in ice-cold buffer, pre-incubated at 37 °C for 10 min, diluted, and centrifuged as before. The final pellet was resuspended in buffer and held on ice for the receptor binding assay.

H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 7/02/08 00- 91

O

0 [0343] For assay, aliquots of the washed membrane preparations and test compounds were incubated for 15 minutes (37 with 0.25 nM 3 HI]spiperone (16.5 Ci.mmol, SNew England Nuclear, Boston, MA) in 50 mM Tris HCI, 120 mM NaCI, 5 mM KCI, 2 mM CaCl 2 1 mM MgC12. The final assay volume was 1.0 ml. The incubations were terminated by rapid filtration through GF/B glass fibre filters using a Brandel filtration manifold. Each tube and filter was then washed three times with 5-ml aliquots of ice- ,0 cold buffer. Specific binding was defined as the total radioligand bound minus that 00 O bound in the presence of 1000 nM butaclamol.

oO Inhibition of cAMP Intracellular Production [0344] The agonist activity of a somatostatin test compound is determined by the following assay.

[0345] CHO-KI cells expressing human somatostatin (SRIF-14) subtype receptors are seeded in 24-well tissue culture plates in RPMI 1640 media with 10% fetal calf serum (FCS).

[0346] Cells at 105 cells/well are washed 2 times by 0.5 ml RPMI 1640 media.

Hank's balanced salt solution supplemented with 0.5mM 3-isobutyl-l-methylxanthine and the cells are incubated for 30 minutes at 37 0 C. Cyclic AMP production is stimulated by the addition of 10 ptM forskolin (Sigma Chemical Co., St.

Louis, MO) for 30 minutes at 37 0

C.

[0347] The agonist effect of a compound is measured by the addition of the test compound (10-10 M to 10 6 M) for five minutes prior to the addition of FSK (10 p.M).

The reaction is terminated by the addition of 500 ul of ice-cold absolute alcohol, and the supernatant is transferred to a 12x75 mm glass tube for cAMP determination, cAMP is measured using radioimmunoassay kit (Perkin-Elmer, Boston, MA).

Other Embodiments [0348] Various modifications and variations of the described method and system of the invention will be apparent to those skilled in the art without departing from the scope and spirit of the invention. Although the invention has been described in connection with specific desired embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments.

H:\MaraR\Keep\Speci\P64463-div-SPECI~doC 7/02/08 00 92 00 0 Indeed, various modifications of the described modes for carrying out the invention that N are obvious to those skilled in the fields of medicine, immunology, pharmacology, Sendocrinology, or related fields are intended to be within the scope of the invention.

[0349] All publications mentioned in this specification, including PCT/US02/17859, are herein incorporated by reference to the same extent as if the disclosure of each independent publication was explicitly provided herein.

In the claims which follow and in the preceding description of the invention, except where the context requires otherwise due to express language or 00 necessary implication, the word "comprise" or variations such as "comprises" or "comprising" is used in an inclusive sense, ie. to specify the presence of the stated features but not to preclude the presence or addition of further features in various embodiments of the invention.

It is to be clearly understood that although prior art publication(s) are referred to herein, this reference does not constitute an admission that any of these documents forms part of the common general knowledge in the art in Australia or in any other country.

H:\araR\Kep\Speci\P64463-div-SPECI.doc 13/02/08

Claims (4)

1. 93- Claims: 1. A method of treating acromegaly in a subject in need thereof, wherein said method comprises administering to said subject a therapeutically effective amount of a chimeric analog, wherein said chimeric analog comprises a compound according to the formula of:. Formula (111), (VI) (VII), (VIII), or as set forth herein; or a pharmaceutically acceptable salt thereof, 00 a compound selected from: Dop2-DPhe-Doc-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Ac-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Ac-DLys(Dop2)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-Lys(Ac)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DLys(Ac)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop3-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop3-Aepa-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, Dop4-Aepa-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, Dop6-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop7-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop8-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop9-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, DopI1 -DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop I11 -DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, DoplI2-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop13 -DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop6-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop7-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop8-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, Dop9-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doC 13/02/08 00
2. 94- Dop I 0-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop 11I -cyclollCys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop I 2-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dopl 13-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop5-D2NaI-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop6-D2Na1-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop7-D2Na1-cyclollCys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop8-D2Na1-cyclollCys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH2, 00 o9DN-yeoCsTrDr-y-aCy]TrN2 ~Dop9I -D2Na-cycloCys-Tyr-DTrp-Lys-Va-Cys] -Thr-NH 2 Dop 1 I-D2NaI-cyclo[Cys-Tyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 Dop 1 2-D2Nal-cyclo[Cys-Tyr-DTrp-Lys-Va-Cys]-Thr-NH 2 Dop 1 2-D2NaI-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys]-Thr-NH 2 Dop I3Da-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 Dop5-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop6-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop7-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop8-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop9I -cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop 1 I0-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dopi 1 -cyclo[Cys-Tyr-DTrp-Lys-VaI-Cys]-Thr-NH 2 Dopl I -cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys]-Thr-NH 2 Dop5-13 -cyclo [Cys-r-DTrp-Lys-I-Cys] -Thr- 2 [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-oI, Dop6-DPhe-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop8-DPhe-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop8-DPhe-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop9I -DPhe-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop 1 IO-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop 11 -DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-oI, Dopl I -DPhe-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop51 Dh-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, H:\MaraR\Keep\Speci\P64463-div-SPECI .doc 13/02/08 00 Dop6-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop7-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop8-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop9-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop I O-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop I1-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop I 2-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop 1 3-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, 00 Dop5-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH2, Dop6-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys)-2Nal-NH 2 Dop7-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop8-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop9-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop 1 O-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2NaI-NH 2 Dop I11 -DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Na-NH 2 Dop I 2-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop 1 3-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 -cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2NaI-NH 2 Dop6-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop7-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop8-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2NaI-NH 2 Dop9-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop 1 O-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop] 1-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2NaI-NH 2 Dopl12-cyclo[Cys-Tyr-DTrp-Lys-Thr-CysI-2Nal-NH 2 Dop13 -cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dopl1-DPhe-cyclo [Cys-31ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop I -Aepa-DPhe-cyclo[Cys-31ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop3 -Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop4-Aepa-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI .doc 13/02/08 I 96 00 Dop3 -DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop4-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 -DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop6-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop7-DPhe-cyclo[Cys-3ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop8-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop9-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH2, Dop 1 O-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 00 Dop I11 -DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop I 2-DPhe-cyc lo [Cys- 3ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop 1 3-DPhe-cyclo (Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop3 -cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop4-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop6-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop7-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop8-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop9-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop 1 0-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Tin-NH 2 Dop 1-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dopl12-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Tin-NH 2 Dop13 -cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop 1 -Caeg-cyclo [DCys-3 PalI-DTrp- Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop2-Caeg-cyc lo [DCys-3 Pal -DTrp-Lys-DCys] -Thir(Bzl)-Tyr-N H2, Dop3-Caeg-cycloI[DCys-3Pa-DTrp-Lys-DCys]-Thr(Bzl)-Tyr-NH2, Dop4-Caeg-cyclo[DCys-3Pal-DTrp-Lys-DCys] -Thr(BzI)-Tyr-NH 2 Dopl1-Aepa-Caeg-cyclo[DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop2-Aepa-Caeg-cyclo[DCys-3 Pal-DTrp-Lys-DCys]-Thr(Bz)-Tyr-NH 2 Dop3 -Aepa-Caeg-cyc lo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(Bz)-Tyr-NH2, Dop4-Aepa-Caeg-cyclo [DCys-3 PalI-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-N H 2 [DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop6-Caeg-cyclo [DCys-3 PalI-DTrp-Lys- DCys] -Thr(Bzl)-Tyr-NH 2 H:\MaraR\Keep\Spci\P64463diV-SPECI .doc 13/02/08 00
3. 97- Dop7-Caeg-cyc lo [DCys-3 Pal -DTrp-Lys-DCys]-Thr(Bzl)-Tyr-NH 2 Dop8-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys]-Thr(Bzl)-Tyr-NH 2 Dop9-Caeg-cyclo[DCys-3 Pal-DTrp-Lys-DCys]-Thr(Bz)-Tyr-NH 2 Dop I O-Caeg-cyclo[DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 DopI I -Caeg-cyclo[DCys-3PaI-DTrp-Lys-DCys]-Thr(Bz)-Tyr-NH 2 DopI 2-Caeg-cyclo[DCys-3Pal-DTrp-Lys-DCys]-Thr(Bz)-Tyr-NH2, DopI 3-Caeg-cycloI[DCys-3Pa1-DTrp-Lys-DCys]-Thr(13zI)-Tyr-NH2, Dop I -Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 00 Dop2-Caeg-cyclollDCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dop3 -Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dop4-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dopl1 -Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr-NH 2 Dop2-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dop3-Aepa-Caeg-cyclollDCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dop4-Aepa-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 -Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr-NH 2 Dop6-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-NH2, Dop7-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-NH 2 Dop8-Caeg-cyclo [DCys-Phe-DTrp- Lys- DCys] -Ser(Bzl)-Tyr-NH 2 Dop9-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dop I O-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-NH2, Dopi 1 -Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-NH2, Dopi. 2-Caeg-cycloI[DCys-Phe-DTrp-Lys-DCys]-Ser(BzI)-Tyr-NH 2 Dop I 3-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-SerBzl)-Tyr-NH2, Dop5 -cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop6-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop7-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH 2 Dop8-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop9-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 DoplO -cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH 2 Dop I11 -cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH 2 Dop I 2-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH 2 HA\MaraR\Keep\Speci\P64463-div-SPECI .doc 13/02/08 00 98 Dopi 3-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 -Thr-NH 2 Dop6-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]l-Thr-NH 2 Dop7-DPhe-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop8-DPhe-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop9-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop 1 O-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop 11 -DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 00 Dop I 2-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dopl 13-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 -cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop6-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop7-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop8-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop9-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dopl 1 -cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop I11 -cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop I 2-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop 13 -cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thir-NH 2 Dop2-Lys(Dop2)-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-DLys(Dop2)-DPhe-cyclo [Cys.-Tyr-DTrp-Lys-Abu-Cys] -Tin-NH 2 Dop2-Lys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Tin- NH 2 Dop2-DLys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Tin- NH 2 Dop2-DLys(Dop2)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Tin-NH 2 Dop I -Lys(DoplI)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Tin-NH 2 Dopl1-Lys(Dopl1)-Aepa-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Th-NH 2 Dop I -Lys(DoplI)-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Tin-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECIdoc 13/02/08 00
4. 99- Dop 1 -Lys(Dop 1 )-Lys-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 Dop 1 -Lys(Dop 1 )-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop 1 -DLys(Dop 1 )-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop 1 -DLys(Dop 1 )-Aepa-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop 1 -DLys(Dop I )-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-N H 2 Dop 1 -DLys(DoplI)-Lys-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 00 Dop I -DLys(Dop I )-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop I -Lys(Dop I )-D2Na1-cyclo [Cys-Tyr-DTrp-Lys-Va -Cys] -Thr-NH 2 Dop 1 -Lys(Dop 1 )-cyclo [Cys-Tyr-DTrp-Lys-Val -Cys] -Thr-NH 2 Dop 1 -Lys(Dop 1 )-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr- NH 2 Dop I -Lys(Dop 1 )-DTyr-DTyr-cyc lo [Cys-Tyr-DTrp-Lys-V al -Cys] -Thr-N H 2 Dop I -Lys(Dop I )-DPhe-cyclo [Cys-Tyr-DTrp- Lys-Thr-Cys]-2Nal -N H2, Dop 1 -Lys(Dop I )-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH2, Dop 1 Lys(Dop 1 )-Lys-DTyr-DTyr-cyc lo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2N al- NH 2 Dop I -Lys(Dop 1 )-DTyr-DTyr-cyclo [C ys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop 1 Lys(Dop I )-DPhe-cyc lo [Cys-Phe-DTrp-Lys -Thr-Cys] -Thr-ol, Dop I -Lys(DoplI)-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop 1 -Lys(Dop 1 )-Lys-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop I -Lys(Dop 1 )-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop 1 -Lys(Dop2)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 DopI -Lys(Dop2)- cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH 2 Dop I -Lys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys]-Trp- NH 2 Dop 1 -Lys(Dop2)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH2, Dop2-Lys(Dop2)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-Aepa-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 H:\MaraR\Keep\Speci\P64463-diV-SPECI .doc 13/02/08 00 100 Dop2-Lys(Dop2)-Lys-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Tin- NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-Aepa-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop2-DLys(Dop2)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-DLys(Dop2)-Aepa-DPhe-cycloIICys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 00 Dop2-DLys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop2-DLys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-Aepa-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop2-Lys(Dop2)-D2Nal-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH2, Dop2-Lys(Dop2)-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Va1-Cys] -Thr- NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Va1-Cys] -Thr-N H 2 Dop2-Lys(Dop2)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys]-2Na-NH2, Dop2-Lys(Dop2)-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2NaI-NH 2 Dop2-Lys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal- NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2NaI-NH 2 Dop2-Lys(Dop2)-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop2-Lys(Dop2)-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop2-Lys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-o1, Dop2-Lys(Dop2)-DTyr-DTyr-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-o, Dop2-Lys(Dop2)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Trp-NH 2 Dop2-Lys(Dop2)- cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Trp-NH 2 Dop2-Lys(Dop2)-Lys-DTyr-DTyr-cycloIICys-Tyr-DTrp-Lys-Va1-Cys]-Trp- NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH2, H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 00 -101 Dop3 -Lys(Dop3)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop3 -Lys(Dop3)-Aepa-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]l-Thr-NH 2 Dop3 -Lys(Dop3)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop3 -Lys(Dop3 )-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop3 -Lys(Dop3)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 NoDop3 -DLys(Dop3 )-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop3 -DLys(Dop3 )-Aepa-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 00 Dp-~sDp)ccoCsTrDr-y-b-y]TrN2 ~Dop3 -DLys(Dop3 )-yDrDr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop3 -DLys(Dop3 )-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop3 -Lys(Dop3)-D2Na1-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH2, Dop3 -Lys(Dop3)-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH2, Dop3 -Lys(Dop3)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr- NH 2 Dop3 -Lys(Dop3)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop3 -Lys(Dop3)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop3 -Lys(Dop3)-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH2, Dop3 -Lys(Dop3)-Lys-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal- NH 2 Dop3 -Lys(Dop3)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2NaI -NH 2 Dop3 -Lys(Dop3 )-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-oI, Dop3 -Lys(Dop3)-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-oI, Dop3 -Lys(Dop3)-Lys-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-oI, Dop3 -Lys(Dop3 )-DTyr-DTyr-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop3 -Lys(Dop3)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 Dop3 -Lys(Dop3)- cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Trp-NH 2 Dop3 -Lys(Dop3 )-Lys-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Trp- NH 2 Dop3 -Lys(Dop3)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 Dop4-Lys(Dop4)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thir-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI .doc 13/02/08 102 00 Dop4-Lys(Dop4)-Aepa-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-Lys(Dop4)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-Lys(Dop4)-Lys-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop4-Lys(Dop4)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-DLys(Dop4)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-DLys(Dop4)-Aepa-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-DLys(Dop4)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 00 Dop4-DLys(Dop4)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop4-DLys(Dop4)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-Lys(Dop4)-D2Na1-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys]-Thr-NH 2 Dop4-Lys(Dop4)-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 Dop4-Lys(Dop4)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Thr- NH 2 Dop4-Lys(Dop4)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop4-Lys(Dop4)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH2, Dop4-Lys(Dop4)-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Na-NH 2 Dop4-Lys(Dop4)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal- NH 2 Dop4-Lys(Dop4)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Na-NH2, Dop4-Lys(Dop4)-DPhe-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-o, Dop4-Lys(Dop4)-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-oI, Dop4-Lys(Dop4)-Lys-DTyr-DTyr-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys-Thr-oI, Dop4-Lys(Dop4)-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop4-Lys(Dop4)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Tmp-NH 2 Dop4-Lys(Dop4)- cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 Dop4-Lys(Dop4)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Trp- NH 2 Dop4-Lys(Dop4)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Trp-NH 2 -Lys(Dop5)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 00 103 TrN 2 [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop5-DLys(Dop5 )-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 2 [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 00 Dop5 -DLys(Dop5)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop5-Lys(Dop5)-D2Na1-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 -Thr-NH 2 [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr- NH 2 -Lys(Dop5)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Va-Cys]1-Thr-NH 2 Dop5 -Lys(Dop5)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 -Lys(Dop5)-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Na-NH 2 Dop5-Lys(Dop5)-Lys-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal- NH 2 [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop5-Lys(Dop5)-DPhe-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-oI, Dop5-Lys(Dop5)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Va-Cys]-Trp-NH2, Dop5-Lys(Dop5)- cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH 2 [Cys-Tyr-DTrp-Lys-VaI-Cys] -Trp- NH 2 [Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 Dop6-Lys(Dop6)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop6-Lys(Dop6)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop6-Lys(Dop6)-Lys-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 00 -104 Dop6-Lys(Dop6)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-N H 2 Dop6-DLys(Dop6)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop6-DLys(Dop6)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop6-DLys(Dop6)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop6-DLys(Dop6)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop6-Lys(Dop6)-D2NaI-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys]-Thr-NH 2 Dop6-Lys(Dop6)-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 00 Dop6-Lys(Dop6)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr- NH 2 Dop6-Lys(Dop6)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop6-Lys(Dop6)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop6-Lys(Dop6)-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop6-Lys(Dop6)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal- NH 2 Dop6-Lys(Dop6)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop6-Lys(Dop6)-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]l-Thr-oI, Dop6-Lys(Dop6)-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop6-Lys(Dop6)-Lys-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-oI, Dop6-Lys(Dop6)-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-oI, Dop6-Lys(Dop6)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 Dop6-Lys(Dop6)- cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH 2 Dop6-Lys(Dop6)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Trp- NH 2 Dop6-Lys(Dop6)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 Dop7-Lys(Dop7)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop7-Lys(Dop7)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop7-DLys(Dop7)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] .Thr-NH 2 Dop7-DLys(Dop7)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop7-Lys(Dop7)-D2Na1-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]l-Thr-NH 2 Dop7-Lys(Dop7)-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 Dop7-Lys(Dop7)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2NaI-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 00 1.05 Dop7-Lys(Dop7)-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop7-Lys(Dop7)-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop7-Lys(Dop7)-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop7-Lys(Dop7)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Va-Cys]-Trp-NH 2 Dop7-Lys(Dop7)- cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 Dop8-Lys(Dop8)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop8-Lys(Dop8)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop8-DLys(Dop8)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 00 Dp-~sDp)ccoCsTrDr-y-b-y]TrN2 ~Dop8-Lys(Dop8)-2a-cyclo [Cys-Tyr-DTrp-Lys-u-Cys] -Thr-NH 2 ~Dop8-Lys(Dop8)-a-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop8-Lys(Dop8)-Dh-cyclo [Cys-Tyr-DTrp-Lys--Cys]-l-NH 2 Dop8-Lys(Dop8)-D-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop8-Lys(Dop8)-Dh-cyclo [Cys--DTrp-Lys-Thr-Cys]-l-, 15Dop8-Lys(Dop8)-D-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, 15Dop8-Lys(Dop8)-cyhc~[ys-Phesy-DTrp-Lys--Cys]-Thr-ol,2 Dop8-Lys(Dop8)-D cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys]-Trp-NH2, Dop8-Lys(Dop8)-D cyclo[Cys-Tyr-DTrp-Lys-A-Cys] Trp-NH 2 Dop9-Lys(Dop9)-D-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys-Thr-NH 2 Dop9-Lys(Dop9)-h-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys-Thr-NH 2 ~Dop9-DLys(Dop9)-D-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop9-Lys(Dop9)2a-cyclo [Cys-Tyr-DTrp-Lys-u-Cys] -Thr-NH 2 Dop9-Lys(Dop9)-a-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop9-Lys(Dop9)-Dh-cyclo [Cys-Tyr-DTrp-Lys--Cys Thr-NH 2 25Dop9-Lys(Dop9)-D-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop9-Lys(Dop9)-cyhcl[ycl-Ty--DTrp-Lys-Thr-Cys] 2Nal-NH, Dop9-Lys(Dop9)-D-cyclo [Cys-Phe-DTrp-.Lys-Thr-Cys] -Thr-ol, Dop9-Lys(Dop9)-Dcyclo[Cys- -DTrp-Lys--Cys]-Thr-ol, 2 Dop9-Lys(Dop9)-D cyclo [Cys-Tyr-DTrp-Lys-Val-Cys-Trp-NH 2 Dop9-Lys(Dop)-D ycl o[Cys-Tyr-DTrp-Lys-Cs]-rp-hr- 2 ~Dop IO-Lys(Dopl1O)-Dh-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 DopI1O-DLys(Dopl )-h-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] Tbr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 00 106 0 Dopl 1 -DLys(Dop I 0)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, Dopi O-Lys(Dopl IO)-D2Na-cyclo[Cys-Tyr-DTrp-Lys-VaI-Cys]-Thr-NH2, Dop 1 0-Lys(Dop I 0)-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys]-Thr-NH 2 Dopl I -Lys(Dop 1 O)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 DopI1O-Lys(Dopl1 )-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 DopI1 -Lys(Dopl1 )-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, DopI1 -Lys(Dopl1 )-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, 00 Dopl I -Lys(Dopl I )-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 Dop I -Lys(Dop 10)- cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH 2 DolI-y(oll-(h-yl[y-y-Np-y-b-y]TrN2 Dop 11 -Lys(Dop 11)-Dh-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop 11 -Lys(Dop 1)-Dh-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dopl 11-DLys(Dop 11)-Dh-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-N H 2 Dop 11 -Lys(Dopl lI)-D2Na1-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys]-Thr-NH2, Dopl 11-Lys(Dopl 11)-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 Dopl 11-Lys(Dop 11).-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2NaI-NH 2 Dop 11 -Lys(Dop 11 )-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop 11 -Lys(Dop 11 )-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop 11 -Lys(Dop 11 )-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dopi 1 -Lys(Dopl 1)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH 2 Dopl 11-Lys(Dop 11)- cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys]-Trp-NH 2 Dopl12-Lys(DoplI2)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, DoplI2-Lys(Dopl12)-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dopl12-DLys(Dopl12)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dopl12-DLys(DoplI2)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dopl12-Lys(Dopl12)-D2NaI-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dopi 2-Lys(Dop 1 2)-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop 1 2-Lys(Dop 1 2)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Thr-CysI-2Nal-NH2, Dop I 2-Lys(Dop 1 2)-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dopi 2-Lys(DopI 2)-DPhe-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-oI, H:\MaraR\Keep\Speci\P64463div-SPECI.doc 13/02/08 00 107 Dop I 2-Lys(Dop 1 2)-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop I 2-Lys(Dop 1 2)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 Dop 1 2-Lys(Dop 12)- cyclo[Cys-Tyr-DTrp-Lys-VaI-Cys]-Trp-NH 2 Dop 1 3-Lys(Dop 1 3)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop I 3-Lys(Dop 1 3)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop 1 3-DLys(Dopl 1 )-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 No Dop 1 3-DLys(Dop 1 3)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 00 Dop 1 3-Lys(Dop 1 3)-D2Na1-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 Dop 1 3-Lys(Dop 1 3)-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Do -y(o )DNeicoCsTrDr-LsTrCs-NlN2 Dop I 3-Lys(Dop 1 3)-Dh-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop 1 3-Lys(Dop 1 3)-Dh-cyclo[Cys--DTrp-Lys-Thr-Cys]-I-NH, Dop 1 3-Lys(Dop 1 3 )-D-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop 1 3-Lys(Dop 1 3)-cyhccl [Cys-Phe -DTrp-Lys--Cys] -Thr-ol, ~Dopl13-Lys(Dopl13)-D cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH 2 Dop I -Lys(Dop 1)-gcyclo [Cys- al-DTrp-Lys-lCys] -TrH 2 r-H Dopl1-Lys(Dopl1)-Caeg-cyclo[DCys-3Pa-DTrp-Lys-DCys] -Tr(Bz)-Tyr-NH 2 Dop 1 -Lys(Dop )-Caeg-cyclo [DCys-Pl-DTrp-Lys-DCys] -er(Bz)-Tyr-, NH- 2 DoplI-DLys(Dopl1)-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bz)-Tyr-NH2, Dop 1 -Lys(Dop I )-Lys-Caeg-cyclo [DCys-3 PalI-DTrp-Lys-DCys] -Thr(BzI)-Tyr- NH 2 Dop I -Lys(Dop 1 )-Lys-Caeg-cyclo [DCys-Phe-DTrp)-Lys-DCys]-Ser(Bzl)-Tyr- NH- 2 Dop I -DLys(Dop I )-Lys-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys]-Thr(Bzl)-Tyr- NH 2 Dop 1 -DLys(Dop 1 )-Lys-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr- NH 2 Dop I -Lys(Dop I )-Aepa-Caeg-cyclo [DCys-3 PalI-DTrp- Lys-DCys] -Thr(Bzl)-Tyr- NH- 2 H:\MaraR\Keep\Speci\P64463div-SPECI .doc 13/02/08 00 108 Dop 1 -Lys(Dop 1 )-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr- NH- 2 Dop I -DLys(DoplI)-Aepa-Caeg-cyclo [DCys-3 Pal -DTrp-Lys- DCys] -Thr(Bz)- Tyr-NH 2 Dop 1 -DLys(Dop 1 )-Aepa-Caeg-cyclollDCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)- Tyr-NH 2 Dop I -Lys(Dop I Lys-Aepa-Caeg-cyclo [DCys-3 PalI-DTrp-Lys-DCys] -Thr(Bzl)- Tyr-NH 2 00 Dopi. -Lys(Dop l)-Lys-Aepa-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(BzI)- Tyr-NH 2 Dop 1 -DLys(Dop 1 )-Lys-Aepa-Caeg-cyclo[DCys-3Pal-DTrp-Lys-DCys]- Thr(Bzl)-Tyr-NH 2 Dop I -DLys(Dop 1 )-Lys-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] Ser(Bzl)-Tyr-NH 2 Dop2-Lys(Dop2)-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys]-Thr(Bz)-Tyr-NH 2 Dop2-Lys(Dop2)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr-NH 2 Dop2-DLys(Dop2)-Caeg-cyc lo [DCys-3 PalI-DTrp-Lys-DCys] -Thr(Bzl)-Tyr- NH 2 Dop2-DLys(Dop2)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-NH2, Dop2-Lys(Dop2)-Lys-Caeg-cyclo[DCys-3 Pal-DTrp-Lys-DCys]-Thr(Bzl)-Tyr- NH 2 Dop2-Lys(Dop2)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr- NH 2 Dop2-DLys(Dop2)- Lys-Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(BzI)-Tyr- NH 2 Dop2-DLys(Dop2)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr- NH 2 Dop2-Lys(Dop2)-Aepa-Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DC ys] -Thr(Bzl)-Tyr- NH- 2 Dop2-Lys(Dop2)-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr- NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 00 109 0 Dop2-DLys(Dop2)-Aepa-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(BzI)- Tyr-NH 2 Dop2-DLys(Dop2)-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)- Tyr-NH 2 Dop2-Lys(Dop2)-Lys-Aepa-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys]-Thr(Bzl)- Tyr-N H 2 Dop2-Lys(Dop2)-Lys-Aepa-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bz)- Tyr-NH 2 00 Dop2-DLys(Dop2)-Lys-Aepa-Caeg-cyclIo [DCys-3 PalI-DTrp-Lys- DCys] Thr(13zi)-Tyr-NH 2 Dop2-DLys(Dop2)-Lys-Aepa-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]- Ser(Bzl)-Tyr-NH 2 Dop3-Lys(Dop3)-Caeg-cyclo[DCys-3 Pal-DTrp-Lys-DCys]-Thr(Bzl)-Tyr-NH2, Dop3 -Lys(Dop3)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-NH2, Dop3 -Lys(Dop3)- Lys-Caeg-cyclo [DCys-3 PalI-DTrp-Lys-DCys] -Thr(BzO-Tyr- NH 2 Dop3 -Lys(Dop3)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr- NH 2 Dop3 -Lys(Dop3)-Aepa-Caeg-cyclo [DCys-3 PaI-DTrp-Lys-DCys] -Thr(BzI)-Tyr- NH 2 Dop3 -Lys(Dop3)-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr- NH- 2 Dop3 -DLys(Dop3 )-Caeg-cyclo [DCys-3 PalI-DTrp-Lys-DCys] -Thr(Bzl)-Tyr- NH- 2 Dop3-DLys(Dop3)-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-NH2, Dop3 -DLys(Dop3)- Lys-Caeg-cycl o[DCys-3 PalI-DTrp- Lys-DCys] -Thr(Bzl)-Tyr- NH- 2 Dop3 -DLys(Dop3)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr- NH 2 Dop3 -DLys(Dop3 )-Aepa-Caeg-cyc lo [DCys-3 Pal- DTrp-Lys-DCys] -Thr(BzI)- Tyr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 00 110 Dop3 -DLys(Dop3)-Aepa-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)- Tyr-NH 2 Dop4-Lys(Dop4)-Caeg-cyclo [DCys-3 PalI-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-N H 2 Dop4-Lys(Dop4)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr-NH 2 Dop4-Lys(Dop4)-Lys-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys]-Thr(Bzl)-Tyr- NH 2 Dop4-Lys(Dop4)-Lys-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCysJ-Ser(Bzl)-Tyr- NH 2 00 ~Dop4-Lys(Dop4)-Aepa-Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DCysJ -Thr(BzI)-Tyr- NH 2 Dop4-Lys(Dop4)-Aepa-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr- NH 2 Dop4-Lys(Dop4)-Lys-Aepa-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys]-Thr(BzI)- Tyr-NH 2 Dop4-Lys(Dop4).-Lys-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)- Tyr-NH 2 Dop4-DLys(Dop4)-Caeg-cyc lo [DCys- 3 PalI-DTrp-Lys-DCys] -Thr(Bzl)-Tyr- NH 2 Dop4-DLys(Dop4)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(BzI)-Tyr-NH 2 Dop4-DLys(Dop4)-Lys-Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(BzI)-Tyr- NH 2 Dop4-DLys(Dop4)-Lys-Caeg-cyclo [DCys-.Phe-DTrp-Lys-DCys]-Ser(BzI)-Tyr- NH- 2 Dop4-DLys(Dop4)-Aepa-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys]-Thr(Bzl)- Tyr-NH 2 Dop4-DLys(Dop4)-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)- Tyr-NI- 2 Dop4-DLys(Dop4)-Lys-Aepa-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys]- Thr(BzI)-Tyr-NH 2 Dop4-DLys(Dop4)-Lys-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] Ser(BzI)-Tyr-NH 2 -Lys(Dop5)-Caeg-cyc lo [DCys-3 Pal -DTr)- Lys-DC ys] -Thr(Bz)-Tyr-N H 2 H:\maraR\Keep\speci\P64463-div-SPECI.doc 13/02/08 00-1 1 -Lys(Dop5)-Caeg-cyclollDCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dop5-DLys(Dop5)-Caeg-cyclo[DCys-3Pal-DTrp-Lys-DCys]-Thr(Bz)-Tyr- NH 2 Dop5-DLys(Dop5)-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys-Ser(Bz)-Tyr-NH2, DopS-Lys(Dop5)-Lys-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(BzI)-Tyr- NH 2 NH 2 00 ~Dop5 -DLys(Dop5)-Lys-Caeg-cyclo [DCys-3 Pal- DTrp-Lys-DCys] -Thr(Bzl)-Tyr- NH4 2 -DLys(Dop5)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr- NH 2 Dop6-Lys(Dop6)-Caeg-cyc lo [DCys-3 Pal -DTrp-Lys-DCys] .Thr(Bzl)-Tyr-N H 2 Dop6-Lys(Dop6)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bz)-Tyr-NH2, Dop6-DLys(Dop6)-Caeg-cyc lo [DCys-3 PalI-DTrp-Lys-DCys] -Thr(BzI)-Tyr- NH 2 Dop6-DLys(Dop6)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dop6-Lys(Dop6)-Lys-Caeg-cyclolDCys-3 Pal-DTrp-Lys-DCys]-Thr(Bzl)-Tyr- NH 2 Dop6-Lys(Dop6)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr- NH 2 Dop6-DLys(Dop6)-Lys-Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(BzI)-Tyr- NH- 2 Dop6-DLys(Dop6)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr- NH- 2 Dop7-Lys(Dop7)-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys]-Thr(Bzl)-Tyr-NH2, Dop7-Lys(Dop7)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr-NH 2 Dop7-Lys(Dop7)-Lys-Caeg-cyclo[DCys-3 PaI-DTrp-Lys-DCys]-Thr(BzI)-Tyr- NH- 2 Dop7-Lys(Dop7)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCysI-Ser(BzI)-Tyr- NH- 2 Dop8-Lys(Dop8)-Caeg-cyclo [DCys-3 PaI-DTrp-Lys-DCys]-Thr(BzI)-Tyr-NH2, H* \MaraR\Keep\Speci\P64463-div-SPECI .doc 13/02/08 00 112 008LsDp)Ce-ycoDy-h-~pLsD~s-e(z)TrN2 Dop8-Lys(Dop8)-LCaeg-cyclo [DCys-P-DTrp-Lys-DCys] -r(Bzl)-Tyr- 2 NH 2 Dop8-Lys(Dop8)-Lys-Caeg-cyclollDCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr- NH 2 Dop9-Lys(Dop9)-Caeg-cyc lo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop9-Lys(Dop9)-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr-NH 2 Dop9-Lys(Dop9)-Lys-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(BzI)-Tyr- 00 NH 2 Dop9-Lys(Dop9)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr- NH 2 Dop I O-Lys(Dop 1 O)-Caeg-cyclollDCys-3 Pal-DTrp-Lys-DCys]l-Thr(BzI)-Tyr- NH 2 Dop I O-Lys(Dopl 1 )-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr- NH 2 Dopl O-Lys(DoplI 0)-Lys-Caeg-cyclo[DCys-3Pal-DTrp-Lys-DCys]-Thr(Bz)- Tyr-NH 2 Dop 1 0-Lys(Dopl I )-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr- NH 2 DopI I -Lys(Dopl 11)-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(BzI)-Tyr- NH 2 Dop I 1 -Lys(Dopl I l)-Caeg-cyclollDCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr- NH 2 DopI I -Lys(Dopl I1)-Lys-Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(BzI)- Tyr-NH 2 Dop 11I -Lys(Dop 11 )-Lys-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr- NH 2 Dop I 2-Lys(Dop I 2)-Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(BzI)-Tyr- NH 2 DopI2-Lys(Dopl 2)-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(BzI)-Tyr- NH 2 IA \MaraR\Keep\Speci\P64463-div-SPECI .doc 13/02/08 00 113 Dop I 2-Lys(Dop 1 2)-Lys-Caeg-cyclo [DCys-3 PalI-DTrp-Lys-DCys] -Thr(BzI)- Tyr-NH 2 Dop 1 2-Lys(Dop I 2)-Lys-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr- NH 2 Dop I 3-Lys(DoplI3)-Caeg-cyclo [DCys-3 Pal- DTrp-Lys-DCys] -Thr(Bz)-Tyr- NH 2 Dop I 3-Lys(Dop 1 3)-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr- NH 2 00 Dop 1 3-Lys(Dop I 3)-Lys-Caeg-cyclo [DCys-3 Pal- DTrp- Lys-DCys] -Thr(BzI)- Tyr-NH- 2 Dop 1 3-Lys(Dop 1 3)-Lys-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr- NH- 2 Dop 1 -Lys(Dop 1 )-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH 2 DoplI -Lys(Dop 1 )-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dopl1 -DLys(Dop 1 )-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop 1 -DLys(Dopl1)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop 1 -Lys(Dop 1 )-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dopi. -DLys(Dopl )-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-CysI-Thr-NH 2 Dop2-Lys(Dop2)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop2-Lys(Dop2)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH 2 Dop2-DLys(Dop2)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop3 -Lys(Dop3)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop3 -Lys(Dop3 )-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop3 -Lys(Dop3)-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop4-Lys(Dop4)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop4-Lys(Dop4)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH2, Dop4-Lys(Dop4)-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 -NH 2 -Lys(Dop5)-DPhe-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 HE\MaraR\Keep\Speci\P64463-div-SPECI .doc 13/02/08 00 114 [Cys-Phe-Phe-DTrp.-Lys-Thr-Phe-Cys]-NH 2 -DLys(Dop5 )-DPhe-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH2, [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop6-Lys(Dop6)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH2, Dop6-Lys(Dop6)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-CysI-Thr-NH 2 No Dop6-DLys(Dop6)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH2, Dop6-DLys(Dop6)-DPhe-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH2, 00 o6LsDp)ccoCsPeN-eDr-y-h-y]TrN2 Dop6-DLys(Dop6)-cyclo [Cys-Phe-(N-Me)DTr-Lys-Thr-Cys] -Thr-NH 2 Dop6-Lys(Dop)-cyclo [Cys-Phe-(Ne-MDTrp-Lys-Thrh-Cys] NH 2 Dop7-Lys(Dop7)-Dh-cyclo [Cys-Phe--DTrp-Lys-Thr-Cys]Th-NH 2 Dop7-Lys(Dop7)-D-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-N H 2 Dop7-Lys(Dop7)-cyclo [Cys-Phe-(N-MDTrp-Lys-ThrPh-Cys]h-NH2, Dop8-Lys(Dop8)-Dh-cyclo [Cys-Phe--DTrp-Lys-Thr -Cys]Th-NH 2 ~Dop8-Lys(Dop8)-D-cyclo [Cys-Phe-N-DTrp-Lys-Thr-Cys] h-NH 2 Dop9-Lys(Dop9)-Dh-cyclo[Cys-Phe--DTrp-Lys-Thr -Cys]Th-NH 2 Dop 1 0-Lys(Dop 1 O)-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop I O-Lys(Dopl 0 )-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]l-Thr-NH 2 Dop I Il-Lys(DoplI 1)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH2, Dopi 1-Lys(Dopl 1 )-DPhe-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH2, Dopi 2-Lys(Dopl2)-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH2, DoplI2-Lys(DoplI2)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop13 -Lys(Dopl13)-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dopl13-Lys(DoplI3)-DPhe-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH2, DoplI-DPhe-cyclo [Cys-3 ITyr(Dopl1)-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop I -DPhe-Doc-DPhe-cyclo [Cys-3 ITyr(Dopl1)-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop I -DLys(Dopl1)-DPhe-cyclo [Cys-31ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop 1 -DLys(DoplI)-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop I -Lys(DoplI)-DTyr-DTyr-cyclo[Cys-31ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 H: \MaraR\Keep\Speci\P64463-div-SPECI .doc 13/02/08 00 115 00l-y(o )Dh-yl[y-3~rDr-y-h-y]TrN2 Dop 1 -Lys(Dopl1)-A-DPhe-cyclo [Cys-31Tyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop I -Lys(Dop)Apah-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop 1 -Lys(Dop I )-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 ~Dop 1 -Lys(Dop I )-yDrDr-cyclo [Cys-3 Tyr-DTrp-Lys-Thr-Cys] -Thr- NH 2 Dop 1 -DLys(Dop 1 )-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop I -DLys(DoplI)-Lys-DTyr-DTyr-cyclo [Cys-31ITyr-DTrp-Lys-Thr-Cys] -Thr- 00 NH 2 Dop I -DLys(DoplI)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop 1 -DLys(DoplI)-Aepa-DPhe-cyclo[Cys-31ITyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop 1 -Lys(DoplI)-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop I -Lys(DoplI)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop I -Lys(Dopl1)-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-CysJ-Thr-NH 2 Dop 1 -DLys(Dopl1)-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop I -Lys(DoplI)-cyclo[Cys-31ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop 1 -Lys(DoplI)-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop I -DLys(DoplI)-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 Dop I -DLys(Dop I )-Lys- DTyr-DTyr-cyclo [Cys-3 I Tyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop 1 -DLys(Dopl1)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop 1 -DLys(DoplI)-Aepa-DPhe-cyclo[Cys-31ITyr-DTrp-Lys-Va-Cys]1-Thr-NH 2 Dop I -Lys(Dopl1)-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop I -Lys(DoplI)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-VaI-Cys]-Thr-NH 2 Dop 1 -Lys(Dopl1)-Aepa-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-VaI-Cys]-Thr-NH 2 Dop I -DLys(Dopl1)-cyclo [Cys-31ITyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dopi -Lys(Dopl1)-cyclo[Cys-31ITyr-DTrp-Lys-Val-Cys]-Thr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECIdoc 13/02/08 00 116 Dop I -Lys(Dop 1 )-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-VaI-Cys] -Thr- NH 2 Dop 1 -DLys(Dop 1 )-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 Dop I -DLys(Dop 1 )-Lys-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr- NH 2 Dop2-DPhe-cyclo[Cys-3 ITyr(Dop2)-DTrp-Lys-Val-Cys] -Thr-NH 2 DNoLsDp)Dy-~r-yl Cs3Iy-~p-y-h-y]TrN 2 0 Dop2-Lys(Dop2)-Aepa-DTyr-Dcyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-2 NH 2 ~Dop2-Lys(Dop2)-DAe-yDr-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr- Dop2-LsDp)Ap-,ecco[y- ~rDr-y-h-y]TrN 2 Dop2-Lys(Dop2)-DPhe-cyclojCys-3 Tyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop2.-Lys(Dop2)-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop2-DLys(Dop2)-Dh-cyclo [Cys-3 Tyr-DTrp-Lys-Thr-Cys-Thr-NH 2 ~Dop2-Lys(Dop2)-eDh-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-Lys(Dop2)Ly-yDr-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr- NHp 2 LsDp)ccoCs3Tr-~pLsTrCs-h- Dop2-Lys(Dop2)-sDTyr-DTyr-cyclo [Cys-3ITyr-DTrp-Lys-Thr-Cys] -Thr- Dop2-DLys(Dop2)-Aepa-DTyr-Dcyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -rN2 Dop2-DLys(Dop2)-Lys-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] TNH 2 Dop2-DLys(Dop2)-Aep-Dyhe~-cyclo [Cys-3 Tyr-DTrp-Lys-u-Cys-Thr- NH 2 25Dop2-Lys(Dop2)-DyrDe-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-p-DPhe-cyclo [Cys-3 Tyr-DTrp-Lys-Abu-Cys] -Thr- Dop2-LsDp)Ap-,eccoCs3 ~rDr-y-b-y]TrN Dop2-Lys(Dop2)yrr-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 H: \MaraR\Keep\Speci\P64463-div-SPECI .doc 13/02/08 117 00 Dop2-Lys(Dop2)-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Tin-NH 2 Dop2-Lys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop2-DLys(Dop2)-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Tin- NH 2 Dop2-DLys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 Dop2-DLys(Dop2)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr-NH 2 00 Dop2-DLys(Dop2)-Aepa-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-VaI-Cys] -Tin-NH 2 Dop2-Lys(Dop2)-DPhe-cyclolCys-3 ITyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-VaI-Cys]-Thr-NH 2 Dop2-DLys(Dop2)-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-cyclo [Cys-3 ITyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys] -Tin- NH 2 Dop2-DLys(Dop2)-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys] -Tin-NH 2 Dop2-DLys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-VaI-Cys] -Tin- NH 2 Dop3 -Lys(Dop3 )-DPhe-cyclo [Cys-3 LTyr-DTrp-Lys-Thr-Cys] -Tin-NH 2 Dop4-Lys(Dop4)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Tin-NH 2 Dop3 -Lys(Dop3)-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Tin-NH 2 Dop4-Lys(Dop4)-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Tin-NH 2 Dop5 -DLys(Dop5)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Tin-NH 2 -Lys(Dop5)-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Tin-NH 2 Dop5-Lys(Dop5)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Th-NH 2 -DLys(Dop5)-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Tin-NH 2 Dop5 -Lys(Dop5)-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Tin-NH 2 [Cys-3 ITyr-DTrp-Lys-Tin-Cys] -Tin- NH 2 H:\MaraR\IKeep\speci\P64463-div-SPECI.doc 13/02/08 00 118 005Dy(o5-~rDy-yl[ys3~rDr-y-h-y]TrN2 Dop5-DLys(Dop5)--DTyr-DTyr-cyclo[Cys-3 Tyr-DTrp-Lys-Thr-Cys] -Thr- 2 NH 2 )-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop5-Lys(Dop5)-DTyr-DTyr-cyclo[Cys-3ITyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 [Cys-3 ITyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 [Cys-3 ITyr-DTrp-Lys.-Abu-Cys] -Thr-NH 2 00 Dop5-Lys(Dop5)-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop5-Lys(Dop5)-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 -DLys(Dop5)-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 -DLys(Dop5)-Lys-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 -DLys(Dop5)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 [Cys-3 ITyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop5-Lys(Dop5)-DPhe-cyclo[Cys-3lTyr-DTrp-Lys-Va-Cys]-Thr-NH2, Dop5-DLys(Dop5)-cyclo[Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr-NH 2 -Lys(Dop5)-cyclo[Cys-3 ITyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop5-Lys(Dop5)-Lys-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr- NH 2 )-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop5-DLys(Dop5)-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Val-CysI-Thr- NH 2 Dop6-Lys(Dop6)-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop7-Lys(Dop7)-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop8-Lys(Dop8)-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop9-Lys(Dop9)-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop 1 O-Lys(Dop 1 0)-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dopl 11-Lys(Dopl 11)-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NI1 2 H:\MaraR\Keep\Speci\P64463-div-SPECI .doc 13/02/08 00 119 Do0 -y(o )ccoCs3 ~rDr-y-h-y)TrN 2 Dop 13 -Lys(Dopl I )-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop6I -Lys(Dop )-~cyclo [Cys-3 Tyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop7-Lys(Dop7)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop8-Lys(Dop8)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH2, Dop9-Lys(Dop9)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop 1 -Lys(Dop I )-DPhe-cyclo [Cys-3ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 NODop 11 -Lys(Dopl 11)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-CysI-Thr-NH 2 0 Dopl I2-Lys(Dopl I )-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 o Dopl13-Lys(Dopl13)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]- Thr-NH 2 ora pharmaceutically acceptable salt thereof, wherein said therapeutically effective amount is the amount effective to treat acromegaly in said patient. 2. The method of claim 1, wherein said chimeric analog comprises a agonist and a dopamine receptor agonist. 3. The method of claim 2, wherein said chimeric analog further comprises a SSTR- 2 agonist. 4. A method of treating hyperprolactinemia in a subject in need thereof, wherein said method comprises administering to said subject a therapeutically effective amount of a chimeric analog, wherein said chimeric analog comprises a compound according to the formnula of: Formula (111), (VI) (VII), (VIII), or as set forth herein; or a pharmaceutically acceptable salt thereof; a compound selected from: Dop2-DPhe-Doc-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Ac-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Ac-DLys(Dop2)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop2-Lys(Ac)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DLys(Ac)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thir-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI .doc 13/02/08 00 120 Dop3-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop3 -Aepa-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop4-Aepa-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop5-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop6-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop7-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop8-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 00 Dop9-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop 1 O-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop I11 -DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop 1 2-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop 1 3-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop6-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop7-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop8-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-N H 2 Dop9-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dopl 1 -cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, Dopi 1 -cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop 1 2-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop 1 3-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 -D2Na1-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop6-D2Na1-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop7-D2Na1-cyclo[Cys-Tyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 Dop8-D2Na1-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop9-D2NaI-cyclo [Cys-.Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop I O-D2NaI-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dopl I -D2NaI-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop 1 2-D2NaI-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dopl 13-D2NaI-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys]-Thr-NH 2 -cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NIH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 00 121 Dop6-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH2, Dop7-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop8-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH2, Dop9-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH2, Dop 1 0-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop I1I -cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop 1 2-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH2, Dopl 13-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 00 Dop6-DPhe-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop7-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop8-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop9-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop I O-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop 11I -DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop 1 2-DPhe-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dopl 13-DPhe-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-oI, [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop6-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop7-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop8-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop9-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop IO-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-oI, Dop I11 -cyclo [Cys-Phe-DTrp-Lys-Thr-Cysl-Thr-oI, Dopl12-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-oI, Dop13 -cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-oI, -2Nal-NH 2 Dop6-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop7-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop8-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Na-NH 2 Dop9-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 DopI1O-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI .doc 13/02/08 00 122 Do 1-0ecco[y-y-Dr-y-h-y]-NlN 2 Dopl I2-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 DoplI -DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 -Dh-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2Na-NH 2 Dop6-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys]-2Na-NH 2 Dop6-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys]-2Na-NH 2 Dop7-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys]-2Na-NH 2 Dop9-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2NaI-NH 2 00 Dop 1 -cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2NaI-NH 2 Dopl 11-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2NaI-NH 2 I -cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 DoplI -cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dopl 1 D-cyclo [Cys- Tyr-DTrp-Lys-Thr-Cys] -hr-NH 2 Dop2 -DPhe-cyclo [Cys-31ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 ~Dop I-A-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop2 -Aepa-DPhe-cyclo [Cys-31ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop3-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop4-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop3 p-DPhe-cyclo [Cys-3 Tyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop4-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 20Dop5-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop6-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop7-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop8-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop9-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop 1p-DPhe-cyclo[Cys-3 Tyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dopi 1 -DPhe-cyclo[Cys-3ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dopl I2-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 DoplI -DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 30Dopl3-Dh-cyclo [Cys-3 Tyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 30Dop4-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 -cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 H.\Maral\Keep\Spveci\P64463-div-SPECI.doc 13/02/08 00 123 Dop6-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop7-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop8-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop9-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop 1 0-cyclo [Cys-31ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop 1 1-cyclo[Cys-31ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 DoplI 2-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop 1 3-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 00 DpI-agccoDy-PlDr-y-~s-h(z)TrN2 Do0 Ce-yl Dy- a-~pLsDy]-h(z)TrN 2 010 Dop2-Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(Bzl)-Tyr-N H 2 Dop3 -Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop4-Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(Bzl)-Tyr-N H 2 Dop I -Aepa-Caeg-cyclo [DCys-3 PaI-DTrp-Lys-DCys]-Thr(BzI)-Tyr-NH 2 Dop2-Aepa-Caeg-cyclo DCys-3 PalI-DTrp-Lys- DCys] -Thr(BzI)-Tyr-N H 2 Dop3 -Aepa-Caeg-cyc lo [DCys-3 Pal-DTrp- Lys- DCys] -Thr(Bz)-Tyr-N H 2 Dop4-Aepa-Caeg-cyc lo [DCys-3 Pal -DTrp- Lys-DCys] -Thr(BzI)-Tyr-N H 2 [DCys-3 Pal -DTrp-Lys-DCys] -Thr(Bzl)-Tyr-N H 2 Dop6-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop7-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop8-Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop9-Caeg-cyclo [DCys-3 PalI-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-N H2, Dop I 0-Caeg-cyclo[DCys-3 Pal-DTrp-Lys-DCys] -Thr(BzI)-Tyr-NH 2 Dop 11I -Caeg-cyclo[DCys-3Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop I 2-Caeg-cyclo[DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop 1 3-Caeg-cyclo[DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop I -Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(BzO)-Tyr-NH 2 Dop2-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(BzI)-Tyr-NH 2 Dop3-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dop4-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr-NH 2 DoplI-Aepa-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bz)-Tyr-NH2, Dop2-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr-NH 2 Dop3-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECT .doc 13/02/08 00 124 0 Dop4-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 -Caeg-cyclo [DCys- Phe-DTrp- Lys- DCys] -Ser(Bzl)-Tyr-NH 2 Dop6-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr-NH 2 Dop7-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bz1)-Tyr-NH4 2 Dop8-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bz)-Tyr-NH 2 Dop9-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-NH 2 Dop I O-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]l-Ser(Bz1)-Tyr-NH2, Dop I1 -Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-NH 2 00 Dop I 2-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-NH2, Dopl 13-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-SerBzl)-Tyr-NH2, -cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop6-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop7-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop8-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop9-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop 1 0-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 DopI 1 -cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH2, Dop I 2-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dopl 13-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop5-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop6-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Tin-NH 2 Dop7-DPhe-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop8-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop9-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH2, Dop 1 0-DPhe-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH2, Dop] I -DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop I 2-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop 1 3-DPhe-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]l-Thr-NH 2 -cyclo [Cys-Phe-.(N-Me)DTrp-Lys-Thr-CysI-Thr-NH 2 Dop6-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH2, Dop7-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop8-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH2, H:\MaraR\Keep\Speci\P64463-div-SPECI .doc 13/02/08 00 125 TnN 2 Dop 1 -cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Tr-NH 2 Dop 1 0-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop I 2-cycloI[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop 13 -cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 5DpLDoplop2)s-cyco y-TyrDTrp-Lys-Ab-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-Lys(Dop2)D-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 00 Dop2-DLys(Dop2)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-Lys-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 Dop2-DLys(Dop2)-Lys-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop2-DLys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]l-Thr-NH 2 Dop 1 -Lys(DoplI)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop I -Lys(Dopl1)-Aepa-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop 1 -Lys(Dopl1)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop 1 -Lys(Dopl1)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 Dop 1 -Lys(Dop 1 )-DTyr-DTyr-cyclojlCys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, Dop 1 -DLys(Dopl1)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Tin-NH 2 Dop I -DLys(Dop I )-Aepa-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop 1 -DLys(Dop I )-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-N H 2 Dop 1 -DLys(Dop I )-Lys-DTyr-DTyr-cyclo [Cys-Tyr- DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop 1 -DLys(Dop 1 )-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop I Lys(Dop 1 )-D2N al-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop I -Lys(Dop 1 )-cyclo [Cys-Tyr-DTrp-Lys-Val -Cys] -Thr-N H 2 Dop 1 -Lys(Dop 1 )-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Va1-Cys] -Tin- NH 2 Dop 1 -Lys(Dop I )-DTyr-DTyr-cyclo [Cys-Tyr- DTrp-Lys-Va1 -Cys] -Thr-NH 2 H:\MaraR\Keep\Sp~eci\P64463-div-SPECI .doc 13/02/08 00 126 Do LsDp1)Dh-yl[y-TrDr.LsTrCs-NlN 2 Dop I -Lys(Dop 1 )-D-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop I -Lys(Dop 1 )-yDrDr-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal- NH 2 Dop I -Lys(Dop 1 )-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop 1 -Lys(Dop 1 )-DPhe-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop I -Lys(Dop 1 )-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop 1 -Lys(Dop 1 )-Lys-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, 00 Dop I -Lys(Dop 1 )-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop I -Lys(Dop2)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-VaI-Cys] -Trp-NH 2 Dop 1 -Lys(Dop2)- cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 Dop 1 -Lys(Dop2)-Lys-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Trp- NH 2 Dop 1 -Lys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH2, Dop2-Lys(Dop2)-DPhe-cycloI[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, Dop2-Lys(Dop2)-Aepa-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-Lys-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]l-Thr- NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-Aepa-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 Dop2-DLys(Dop2)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-Aepa-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, Dop2-DLys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop2-DLys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-Aepa-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 Dop2-Lys(Dop2)-D2Na1-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys]-Thr-NH 2 H:\araR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 00 127 0 Dop2-Lys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Thr- NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop2-Lys(Dop2)-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop2-Lys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal- NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys-2Na-NH2, 00 Dop2-Lys(Dop2)-DPhe-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-oI, Dop2-Lys(Dop2)-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-oI, Dop2-Lys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-oI, Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-oI, Dop2-Lys(Dop2)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH2, Dop2-Lys(Dop2)- cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH2, Dop2-Lys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Trp- NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH2, Dop3 -Lys(Dop3)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop3 -Lys(Dop3)-Aepa-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop3-Lys(Dop3)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop3 -Lys(Dop3)-Lys-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop3 -Lys(Dop3 )-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop3-DLys(Dop3 )-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop3 -DLys(Dop3 )-Aepa-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop3 -DLys(Dop3 )-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop3 -DLys(Dop3 )-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 Dop3-DLys(Dop3)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop3 -Lys(Dop3)-D2Na1-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop3 -Lys(Dop3)-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECT .doc 13/02/08 00 128 Dop3 -Lys(Dop3)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr- NH 2 Dop3 -Lys(Dop3)-DTyr-DTyr-cycloICys-Tyr-DTrp-Lys-Va-Cys]-Thr-NH2, Dop3 -Lys(Dop3)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop3 -Lys(Dop3)-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop3 -Lys(Dop3)-Lys-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal- NH 2 Dop3 -Lys(Dop3)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 00 Dop3 -Lys(Dop3)-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop3 -Lys(Dop3 )-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop3 -Lys(Dop3)-Lys-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop3 -Lys(Dop3)-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop3 -Lys(Dop3)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Trp-NH 2 Dop3 -Lys(Dop3)- cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH 2 Dop3 -Lys(Dop3)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys]-Trp- NH 2 Dop3 -Lys(Dop3)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH 2 Dop4-Lys(Dop4)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-Lys(Dop4)-Aepa-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop4-Lys(Dop4)-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-Lys(Dop4)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 Dop4-Lys(Dop4)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-DLys(Dop4)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-DLys(Dop4)-Aepa-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-DLys(Dop4)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-DLys(Dop4)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 Dop4-DLys(Dop4)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop4-Lys(Dop4)-D2Na1-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop4-Lys(Dop4)-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 00 -129 Dop4-Lys(Dop4)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr- NH 2 Dop4-Lys(Dop4)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH2, Dop4-Lys(Dop4)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2NaI-NH 2 Dop4-Lys(Dop4)-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop4-Lys(Dop4)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal- No NH 2 0 00 Dop4-Lys(Dop4)-DPhe-cyclo[Cys-Phe-DTrp-Lys-Thr-CysI-Thr-o, Dop4-Lys(Dop4)-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop4-Lys(Dop4)-Lys-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-oI, Dop4-Lys(Dop4)-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop4-Lys(Dop4)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Trp-NH 2 Dop4-Lys(Dop4)- cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH 2 Dop4-Lys(Dop4)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Trp- NH 2 Dop4-Lys(Dop4)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys]-Trp-NH2, DopS -Lys(Dop5)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop5 -Lys(Dop5)-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 -DLys(Dop5)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, Dop5-DLys(Dop5)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 -Thr- NH 2 )-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop5-Lys(Dop5)-D2Na1-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 DopS -Lys(Dop5)-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr- NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13102/08 130 00 Dop5-Lys(Dop5)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH2, [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Na-NH2, -2Nal-NH 2 [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal- NH 2 -Lys(Dop5)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 -Lys(Dop5)-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, 00 Dop5 -Lys(Dop5)-Lys-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-oI, Dop5-Lys(Dop5)-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, [Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 -Lys(Dop5)- cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]l-Trp-NH2, -Lys(Dop5)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Trp- NH 2 Dop5-Lys(Dop5)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Trp-NH 2 Dop6-Lys(Dop6)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop6-Lys(Dop6)-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]l-Thr-NH2, Dop6-Lys(Dop6)-Lys-DTyr-DTyr-cyclo [Cys-.Tyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop6-Lys(Dop6)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop6-DLys(Dop6)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop6-DLys(Dop6)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, Dop6-DLys(Dop6)-Lys-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 Dop6-DLys(Dop6)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop6-Lys(Dop6)-D2Nal-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH2, Dop6-Lys(Dop6)-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop6-Lys(Dop6)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr- NH 2 Dop6-Lys(Dop6)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 Dop6-Lys(Dop6)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop6-Lys(Dop6)-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 00 131 Dop6-Lys(Dop6)-Lys-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys]-2Na- NH 2 Dop6-Lys(Dop6)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop6-Lys(Dop6)-DPhe-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop6-Lys(Dop6)-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop6-Lys(Dop6)-Lys-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop6-Lys(Dop6)-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop6-Lys(Dop6)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Va-Cys]-Trp-NH2, 00 Dp-y(o6-ccoCsTrDr-y-a-y]TpN2 ~Dop6-Lys(Dop6)-Ly- -~rcyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Trp- NH 2 Dop6-Lys(Dop6)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys]-Trp-NH 2 Dop7-Lys(Dop7)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, Dop7-Lys(Dop7)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop7-DLys(Dop7)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop7-DLys(Dop7)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop7-Lys(Dop7)-D2Na1-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys]-Thr-NH 2 Dop7-Lys(Dop7)-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop7-Lys(Dop7)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH2, Dop7-Lys(Dop7)-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop7-Lys(Dop7)-DPhe-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop7-Lys(Dop7)-cyclollCys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop7-Lys(Dop7)-DPhe-cyclolCys-Tyr-DTrp-Lys-Val-Cys]j-Trp-NH2, Dop7-Lys(Dop7)- cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Trp-NH 2 Dop8-Lys(Dop8)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop8-Lys(Dop8)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, Dop8-DLys(Dop8)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop8-DLys(Dop8)-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop8-Lys(Dop8)-D2Na1-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH2, Dop8-Lys(Dop8)-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 Dop8-Lys(Dop8)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop8-Lys(Dop8)-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 00 132 Do8LsDp)Dh-yl CsPeDr-y-h-y]-h-l Dop8-Lys(Dop8)-Dh-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-o Dop8-Lys(Dop8)-D-cyclo [Cys-yr-DTrp-Lys-al-Cys]-Trp-NH 2 Dop8-Lys(Dop8)-D cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 ~Dop9-Lys(Dop9)-D cyclo[Cys-Tyr-DTrp-Lys-a-Cys] -hr-NH 2 Dop9-Lys(Dop9)-Dh-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop9-Lys(Dop9)-Dh-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop9-DLys(Dop9)-Dh-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 00 Dop9-Lys(Dop9)2-cyclo[Cys-Tyr-DTrp-Lys-VI-Cys]-Thr-NH2, 0 Dop9-Lys(Dop9)-a-cyclo [Cys-Tyr-DTrp-Lys-Val -Cys]-Thr-NH 2 10Dop9-Lys(Dop9)-D-cyclo [Cys-Tyr-DTrp-Lys-hr-Cys]-2aI-NH 2 Dop9-Lys(Dop9)-Dh-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop9-Lys(Dop9)-D-cyclo [Cys-he-DTrp-Lys-Thr-Cys]-Thr-l, Dop9-Lys(Dop9)-Dh-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, ~Dop9-Lys(Dop9)-D-cyclo [Cys-yr-DTrp-Lys-al-Cys]-Trp-NH, Dop9-Lys(Dop9)-D cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 Dop 1 -Lys(Dop I cclo[Cys-Tyr-DTrp-Lys- A buys-Cy-Hr-H2 DopI1O-Lys(Dopl1 )-Dh-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop IO-Lys(Dop1O)-h-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop IO-DLys(Dop 1 )-Dh-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, 20DopI1O-DLys(DoplO)a-cyclo[Cys-Tyr-DTrp-Lys-al-Cys] -Thr-NH 2 DopI1O-Lys(Dopl1 )D2a-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop IO-Lys(DoplIO)-Dh-cyclo [Cys-Tyr-DTrp-Lys-hr-Cys]-2aI-NH 2 Dop IO-Lys(DoplI )-Dh-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 IO-Lys(DoplIO)-Dh-cyclo [Cys-he-DTrp-Lys-Thr-Cys]-Thr-l, DopI1O-Lys(DoplI )-Dh-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-o Dop IO-Lys(DoplIO)-Dh-cyclo[Cys-yr-DTrp-Lys-al-Cys] rp-NH 2 DopI1 -Lys(Dop 10)-D cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 ~DopI11-Lys(Dopl11)-D cyclo [Cys-Tyr-DTrp-Lys-A-Cys] -hr-NH 2 Dopl I-Lys(Dop Ii)-Dh-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dopl I -Lys(Dop 1)--cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 H:\Mar&R\Keep\Speci\P64463-div-SPECI.doc 13/02/08 00 133 Do 1-0sDp1 -yl Cs-y-~pLsAuCs TrN 2 Dop 11-Lys(Dopl 1)Da-cyclo[Cys-Tyr-DTrp-Lys-Vl-Cys] -Thr-NH 2 Dop 11I -Lys(Dop 11 )-2a-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 ~Dop 11I -Lys(Dop 11 l)-D-cyclo [Cys-Tyr-DTrp-Lys-hr-Cys]-2al-NH 2 Dop I11 -Lys(Dop 1I l)-D-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop I11 -Lys(Dop 11 )-Dc-yco[C[C-y--DTrp-Lys-Thr-Cys]-Thr-l, Dop I1 -Lys(Dopl 11)-cyhcl o[Cys-Phe-DTrp-Lys-Thr-Cys] Thr-oI, 00 ~Dopl 11-Lys(Dop 11)-Dh-cyclo[Cys-yr-DTrp-Lys-al-Cys] rp-NH, 0 Dopl 11-Lys(Dop 11)-D cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 I 2-Lys(Dop I I)-D cyclo [Cys-Tyr-DTrp-Lys-A-Cys] -hr-NH 2 DoplI2-Lys(DoplI2)-Dh-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dopl12-Lys(DopI2)-h-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dopl12-DLys(DoplI2)-Dh-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 ~DoplI2-Lys(Dopl2)Da-cyclo [Cys-Tyr-DTrp-Lys-al-Cys] -Thr-NH 2 DoplI2-Lys(DoplI2)-2a-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dopl12-Lys(Dopl12)-Dh-cyclo [Cys-Tyr-DTrp-Lys-hr-Cys]-2aI-NH 2 Dopl12-Lys(Dopl12)-Dh-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Na-NH 2 Dopl12-Lys(Dopl12)-Dh-cyclo [Cys-he-DTrp-Lys-Thr-Cys] -Thr-o12, Dopl12-Lys(Dopl12)-Dh-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, 20DoplI2-Lys(Dopl12)-Dh-cyclo [Cys-yr-DTrp-Lys-al-Cys] rp-NH 2 DoplI2-Lys(Dop 12)-D cyclo [Cys-Tyr-DTrp-Lys-Va-Cys]-Trp-NH 2 Dopl13-Lys(Dopl1 cyclo [Cys-Tyr-DTrp-Lys-Au-Cys] -hr-NH 2 Dop13 -Lys(DoplI3)-Dh-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 ~Dop 13-Lys(Dop1 )-h-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop13 -DLys(Dopl13)-D-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop 13 -Lys(Dop13)a-cyclo[Cys-Tyr-DTrp-Lys-VI-Cys] -Thr-NH 2 Dop13 -Lys(DoplI3)-2a-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 ~Dop13-Lys(Dop13)-D-cycoICys-Tyr-DTrp-Lys-hr-Cys]-2a1-NH2, Dop13 -Lys(DoplI3)-Dh-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop13 -Lys(Dop13 )-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]1-Thr-oI, H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 00 134 DopI 13-Lys(Dop 1 3)-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop 1 3-Lys(Dop 1 3)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 DoplI3-Lys(Dop 13)- cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH 2 Dop I -Lys(Dop I )-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(BzI)-Tyr-NH 2 Dop I -Lys(Dop I )-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dop 1 -D Lys(Dop 1 )-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(BzI)-Tyr- NH 2 Dop 1 -DLys(Dop 1 )-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 00 ~Dop 1 -Lys(Dop I )-Lys-Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(Bzl)-Tyr- NH 2 Dop 1 -Lys(Dop I Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr- NH 2 Dop 1 -D Lys(Dop 1 )-Lys-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr- NH 2 Dop 1 -DLys(Dop 1 )-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr- NH 2 Dop I -Lys(Dop I )-Aepa-Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(Bzl)-Tyr- NH 2 Dop I -Lys(Dop 1 )-Aepa-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys)-Ser(BzI)-Tyr- NH 2 Dop I -DLys(Dop 1 )-Aepa-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)- Tyr-NH 2 Dop 1 -DLys(Dop I )-Aepa-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)- Tyr-NH 2 Dop I -Lys(Dop l)-Lys-Aepa-Caeg-cyclo[DCys-3Pal-DTrp-Lys-DCys]-Thr(Bzl)- Tyr-NH 2 Dop 1 -Lys(Dop I )-Lys-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)- Tyr-NH 2 Dop 1 -DLys(Dop 1 )-Lys-Aepa-Caeg-cyclo[DCys-3 Pal-DTrp-Lys-DCys]- Thr(Bzl)-Tyr-NH 2 Dop 1 -DLys(Dop 1 )-Lys-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] Ser(Bzl)-Tyr-NH 2 H:\MaraR\Keep\speci\P64463-div-SPECI.doc 13/D2/08 00 -135 Dop2-Lys(Dop2)-Caeg-cyc lo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop2-Lys(Dop2)-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-NH2, Dop2-D Lys(Dop2)-Caeg-cyclo [DCys-3 Pal- DTrp- Lys-DCys] -Thr(Bzl)-Tyr- NH 2 Dop2-DLys(Dop2)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-NH 2 Dop2-Lys(Dop2)-Lys-Caeg-cyclo[DCys-3 Pal-DTrp-Lys-DCys]-Thr(Bzl)-Tyr- NH 2 Dop2-Lys(Dop2)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(BzI)-Tyr- 00 NH 2 Dop2-DLys(Dop2)-Lys-Caeg-cyclo [DCys-3Pal-DTrp-Lys-DCys] -Thr(BzI)-Tyr- NH 2 Dop2-DLys(Dop2)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr- NH 2 Dop2-Lys(Dop2)-Aepa-Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(BzI)-Tyr- NH 2 Dop2-Lys(Dop2)-Aepa-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr- NH 2 Dop2-DLys(Dop2)-Aepa-Caeg-cyclo [DCys-3 Pal- DTrp-Lys-DCys] -Thr(BzI)- Tyr-NH 2 Dop2-DLys(Dop2)-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(BzI)- Tyr-NH 2 Dop2-Lys(Dop2)-Lys-Aepa-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(BzI)- Tyr-NH 2 Dop2-Lys(Dop2)-Lys-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)- Tyr-NH 2 Dop2-DLys(Dop2)-Lys-Aepa-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] Thr(BzI)-Tyr-NH 2 Dop2-DLys(Dop2)-Lys-Aepa-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]- Ser(Bzl)-Tyr-NH 2 Dop3 -Lys(Dop3)-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys]-Thr(Bzl)-Tyr-NH 2 Dop3 -Lys(Dop3)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bz)-Tyr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI .doc 13/02/08 00 136 Dop3 -Lys(Dop3)-Lys-Caeg-cyclo[DCys-3 Pal-DTrp-Lys-DCys]-Thr(BzI)-Tyr- NH 2 Dop3 -Lys(Dop3)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(BzI)-Tyr- NH 2 Dop3 Lys(Dop3)-Aepa-Caeg-cyclo [DCys-3 Pal- DTrp-Lys-DCys] -Thr(Bzl)-Tyr- NH 2 Dop3 -Lys(Dop3 )-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr- NH 2 00Dop3 -DLys(Dop3 )-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr- NH 2 Dop3 -DLys(Dop3)-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bz)-Tyr-NH2, Dop3 -DLys(Dop3)-Lys-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(BzI)-Tyr- NH- 2 Dop3 -DLys(Dop3 )-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr- NH 2 Dop3 -DLys(Dop3)-Aepa-Caeg-cyclo [DCys-3 Pal -DTrp-Lys- DCys] -Thr(BzI)- Tyr-NH 2 Dop3-DLys(Dop3 )-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(BzI)- Tyr-NH 2 Dop4-Lys(Dop4)-Caeg-cyclo [DCys-3 Pa1-DTrp-Lys-DCys]~-Thr(Bzl)-Tyr-NH2, Dop4-Lys(Dop4)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dop4-Lys(Dop4)- Lys-Caeg-cycl o[DCys-3 PalI-DTrp-Lys-DCys] -Thr(BzI)-Tyr- NH 2 Dop4-Lys(Dop4)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr- NH- 2 Dop4-Lys(Dop4)-Aepa-Caeg-cyclo [DCys-3 PalI-DTrp-Lys-DCys] -Thr(BzI)-Tyr- NH- 2 Dop4-Lys(Dop4)-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(BzI)-Tyr- NH- 2 Dop4-Lys(Dop4)-Lys-Aepa-Caeg-cyclo [DCys-3 PalI-DTrp- Lys-DCys] -Thr(BzI)- Tyr-NI- 2 H: \Maraa\Keep\Speci\P64463-div-SPECI .doc 13/02/08 00 137 Dop4-Lys(Dop4)-Lys-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(BzI)- Tyr-NH 2 Dop4-DLys(Dop4)-Caeg-cyclo [DCys-3Pal-DTrp-Lys-DCys]-Thr(BzI)-Tyr- NH 2 Dop4-DLys(Dop4)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr-NH 2 Dop4-DLys(Dop4)-Lys-Caeg-cyclo [DCys-3 PalI-DTrp-Lys-DCys] -Thr(BzI)-Tyr- NH 2 Dop4-DLys(Dop4)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr- 00 NH 2 Dop4-D Lys(Dop4)-Aepa-Caeg-cyclo [DCys-3 PalI-DTrp-Lys-DCys] -Thr(Bzl)- Tyr-NH 2 Dop4-DLys(Dop4)-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)- Tyr-NH 2 Dop4-DLys(Dop4)-Lys-Aepa-Caeg-cyclo [DCys-3 PalI-DTrp- Lys- DCys] Thr(Bzl)-Tyr-NH 2 Dop4-DLys(Dop4)-Lys-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]- Ser(BzI)-Tyr-NH 2 -Lys(Dop5)-Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop5-Lys(Dop5).-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bz)-Tyr-NH2, Dop5 -DLys(Dop5)-Caeg-cyclo [DCys-3 Pal- DTrp- Lys-DCys] -Thr(Bzl)-Tyr- NH 2 )-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bz)-Tyr-NH 2 -Lys(Dop5)-Lys-Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(Bzl)-Tyr- NH 2 Dop5 -Lys(Dop5)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(BzI)-Tyr- NH- 2 -DLys(Dop5 )-Lys-Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(Bzl)-Tyr- NH1 2 NH 2 Dop6-Lys(Dop6)-Caeg-cyc lo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop6-Lys(Dop6)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr-NH 2 14\MaraR\Keep\Speci\P64463-div-SPECI .doc 13/02/08 00 138 Dop6- DLys(Dop6)-Caeg-cyclo [DCys-3 Pal -DTrp-Lys- DCys] -Thr(Bzl)-Tyr- NH- 2 Dop6-DLys(Dop6)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bz)-Tyr-NH 2 Dop6-Lys(Dop6)-Lys-Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(BzI)-Tyr- NH 2 Dop6-Lys(Dop6)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr- NH 2 Dop6-DLys(Dop6)- Lys- Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DC ys] -Thr(Bzl)-Tyr- 00 NH 2 Dop6-DLys(Dop6)-Lys-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr- NH 2 Dop7-Lys(Dop7)-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(BzI)-Tyr-NH 2 Dop7-Lys(Dop7)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bz)-Tyr-NH 2 Dop7-Lys(Dop7)-Lys-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(BzI)-Tyr- NH 2 Dop7-Lys(Dop7)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr- NH 2 Dop8- Lys(Dop8)-Caeg-cyc lo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(Bz)-Tyr-N H2, Dop8-Lys(Dop8)-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-NH2, Dop8 -Lys(Dop 8)-Lys-Caeg-cyclo [DCys-3 PalI-DTrp- Lys-DCys] -Thr(Bzl)-Tyr- NH 2 Dop8-Lys(Dop8)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr- NH 2 Dop9.-Lys(Dop9)-Caeg-cyclo [DCys-3 PaI-DTrp-Lys-DCys]-Thr(Bzl)-Tyr-NH 2 Dop9-Lys(Dop9)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-NH2, Dop9-Lys(Dop9)-Lys-Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(Bzl)-Tyr- NH 2 Dop9-Lys(Dop9)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr- NH 2 Dop 1 O-Lys(Dop 1 O)-Caeg-cyclo [DCys-3 PalI-DTrp-Lys-DCys] -Thr(Bzl)-Tyr- NH- 2 H:\MaraR\Keep\Speci\P64463-div-SPECI .doc 13/02/08 139 00 DoplI O-Lys(Dop I 0)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr- NH- 2 Dop I O-Lys(Dopl I )-Lys-Caeg-cyclo [DCys-3 Pal- DTrp-Lys-DC ys] -Thr(Bzl)- Tyr-NH 2 Dop I O-Lys(Dop 1 O)-Lys-Caeg-cyclollDCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr- NH 2 Dop I I -Lys(Dopl I l)-Caeg-cyclo[DCys-3Pal-DTrp-Lys-DCys]-Thir(Bzl)-Tyr- NH 2 00 Dop I11 -Lys(Dop 11 )-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr- NH 2 DopI 11-Lys(Dopl 11)-Lys-Caeg-cyclo[DCys-3Pal-DTrp-Lys-DCys]-Thr(BzI)- Tyr-NH 2 Dop I I -Lys(Dop 11 )-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(BzI)-Tyr- NH 2 Dop 1 2-Lys(Dop I 2)-Caeg-cyclo [DCys-3 PalI-DTrp-Lys-DCys] -Thr(Bzl)-Tyr- NH 2 Dop I 2-Lys(Dop 1 2)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr- NH- 2 Dop I 2-Lys(Dopl 2)-Lys-Caeg-cyclo [DC ys-3 Pal- DTrp-Lys-DCys] -Thr(BzI)- Tyr-NH- 2 Dop 1 2-Lys(Dop I 2)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr- NH 2 Dop 1 3-Lys(Dop 1 3)-Caeg-cyc lo [DCys-3 PalI-DTrp- Lys-DCys] -Thr(Bzl)-Tyr- NH 2 Dop I 3-Lys(DopI 3)-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr- NH 2 Dopi. 3-Lys(Dopl 3)-Lys-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DC ys] -Thr(Bz)- Tyr-NH 2 Dop I 3-Lys(DoplI3)-Lys-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bz)-Tyr- NH- 2 DoplI -Lys(DoplI)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop 1 -Lys(Dopl1)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Tr-NH 2 H: \MaraR\Keep\Speci\P64463-div-SPECI .doc 13/02/08 00 -140 Dop 1 -DLys(Dop 1 )-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH 2 Dop I -DLys(DoplI)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop 1 -Lys(DoplI)-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop I -DLys(Dop 1 )-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop2-Lys(Dop2)-DPhe-cyclollCys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-cyclollCys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH 2 Dop2-DLys(Dop2)-DPhe-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 00 Dop2-Lys(Dop2)-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop3-Lys(Dop3)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop3-Lys(Dop3)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys)-Thr-NH 2 Dop3-Lys(Dop3)-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH2, Dop4-Lys(Dop4)-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop4-Lys(Dop4)-DPhe-cyclollCys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop4-Lys(Dop4)-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH 2 -Thr-NH 2 [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH 2 Dop5-DLys(Dop5)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH2, -Thr-NH 2 [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop6-Lys(Dop6)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop6-Lys(Dop6)-DPhe-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-N H 2 Dop6-DLys(Dop6)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH 2 Dop6-DLys(Dop6)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop6-Lys(Dop6)-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop6-DLys(Dop6)-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop7-Lys(Dop7)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH 2 Dop7-Lys(Dop7)-DPhe-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop7-Lys(Dop7)-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop8-Lys(Dop8)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 HA\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 00 141 0o8LsDp)Dh-yl[y-h-NM)~pLsTrCs TrN 2 Dop9-Lys(Dop9)-Dh-cyclo [Cys-Phe--DTrp-Lys-Thr -Cys] Th-NH 2 Dop9-Lys(Dop9)-D-cyclo [Cys-Phe- -DTrp-Lys-Thr -Cys] h-NH 2 Dop 1 -Lys(Dop 1 )-~cyclo[Cysh-Phe-N-DTrp-Lys-Thr-Cys] -H 2 ,H2 ~Dop I O-Lys(Dop 1 O)-Dh-cyclo [Cys-Phe-N-DTrp-Lys-Thr-Cys]h-NH 2 ~Dopl 11-Lys(Dop 11 0)-D-cyclo [Cys-Phe--DTrp-Lys-Thr-Cys]h-NH 2 Dopl 11-Lys(Dop 11)-Dh-cyclo [Cys-Phe-N-DTrp-Lys-Thr -Cys] h-NH 2 Dopl I 2-Lys(Dop I )-Dh-cyclo[Cys-Phe--DTrp-Lys-Thr-Cys]Th-NH 2 00l-y(ol)ccl[y-h-h-~pLy-h-h-y]N2 00DoplI2-Lys(Dopl12)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop13 -Lys(DoplI3)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dopl13-Lys(Dopl13)-DPhe-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH2, Dopl1-DPhe-cyclo[Cys-3 ITyr(DoplI)-DTrp-Lys-Val-Cys]-Thr-NH 2 Dopl1-DPhe-Doc-DPhe-cyclo [Cys-3 ITyr(DoplI)-DTrp-Lys-Val-Cys] -Thr-NH 2 Dopl1-DLys(Dopl1)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dopl1-DLys(DoplI)-Aepa-DPhe-cyclo[Cys-31ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dopl1-Lys(Dopl1)-DTyr-DTyr-cyclo [Cys-31ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dopl1-Lys(DoplI)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 DoplI-Lys(DoplI)-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dopl1-DLys(Dopl1)-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dopl1-Lys(DoplI)-cyclo [Cys-31ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop 1 -Lys(Dop 1 )-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-CysJ-Thr- NH 2 Dop 1 -DLys(Dop 1 )-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop I -DLys(Dop I )-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr- NH 2 Dop I -DLys(Dop 1 )-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop 1 -DLys(Dop 1 )-Aepa-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop I -Lys(Dopl1)-DTyr-DTyr-cyclo [Cys-31ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 00 142 Dop I -Lys(Dopl1)-DPhe-cyclo[Cys-31ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop I -Lys(Dopl1)-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop 1 -DLys(Dopl1)-cyclollCys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop 1 -Lys(DoplI)-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop 1 -Lys(Dop I)-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 Dop 1 -DLys(Dopl1)-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 00 Dop 1 -DLys(Dop I )-Lys- DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp- Lys-Abu-Cys] -Thr- NH 2 Dop I -DLys(Dopl1)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop I -DLys(DoplI)-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop I -Lys(Dopl1)-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dopi -Lys(DopI)-DPhe-cyclolCys-3ITyr-DTrp-Lys-Va-Cys]-Thr-NH2, Dop 1 -Lys(DoplI)-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop 1 -DLys(Dop 1 )-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop I -Lys(DoplI)-cyclo[Cys-3 ITyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 Dop I -Lys(Dop 1 )-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr- NH 2 Dop 1 -DLys(Dop 1 )-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 Dop 1 -DLys(Dop 1 )-Lys-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr- NH 2 Dop2-DPhe-cyclo[Cys-3 ITyr(Dop2)-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-Aepa-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr- NH 2 Dop2-Lys(Dop2)-DPhe-cyclolCys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/OR 00 143 0o2Dy(o2-eaDh-yl Cs3Iy-~pLsTrCs TrN 2 Dop2-DLys(Dop2)-eDh-cyclo [Cys-3 Tyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-cycloCys-3 Tyr-DTrp-Lys-Thr-Cys] -Th-NH 2 Dop2-Lys(Dop2)Ly-rDr-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr- NH 2 Dop2-DLys(Dop2)-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 NoDop2-DLys(Dop2)-Aepa-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] Thr-NH 2 00 Dop2-DLys(Dop2)-Lys-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr- NH 2 Dop2-DLys(Dop2)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-3 TTyr-DTrp-Lys-Abu-Cys] -Tin-NH 2 Dop2-Lys(Dop2)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-N H 2 Dop2-Lys(Dop2)-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Tin-NH 2 Dop2-Lys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 Dop2-DLys(Dop2)-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop2-DLys(Dop2)-Lys-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 Dop2-DLys(Dop2)-DPhe-cyclolCys-3 ITyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop2-DLys(Dop2)-Aepa-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-DPhe-cyclo[Cys-3ITyr-DTrp-Lys-Val-Cys]-Th-NH2, Dop2-Lys(Dop2)-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop2-DLys(Dop2)-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr-NH 2 ii:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 00 144 2 Dop2-Lys(Dop2)LyDrDy-cyclo [Cys-3 ITyr-DTrp-Lys-VaI-Cys-Thr- NH 2 Dop2-DLys(Dop2)-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr-NH2, Dop2-DLys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-VaI-Cys]-Thr- NH 2 Dop3 -Lys(Dop3)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop4-Lys(Dop4)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 00 Dop3 -Lys(Dop3)-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop4-Lys(Dop4)-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-N H 2 Dop5-Lys(Dop5)-DPhe-cyclolCys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop5-DLys(Dop5)-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop5-Lys(Dop5)-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr- NH 2 Dop5-DLys(Dop5)-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop5-DLys(Dop5)-Lys-DTyr-DTyr-cyclo[Cys-3 lTyr-DTrp-Lys-Thr-Cys]-Thr- NH 2 )-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop5-Lys(Dop5)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop5-Lys(Dop5)-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop5-DLys(Dop5)-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI .doc 13/02/08 00 145 Dop5-DLys(Dop5)-Lys-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 )-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr-NH 2 [Cys-3 lTyr-DTrp-Lys-Val-Cys]-Thr-NH 2 5o5LsDp)Dh-yl[y-I~rDr-y-a-y]TrN2 [Cys-3 Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 0o5Dy(o5-yl Cs3Iy-~pLsVlCs TrN 2 -Lys(Dop5)-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr-NH 2 00 Dop5-Lys(Dop5)-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr- NH 2 Dop5-DLys(Dop5)-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-VaI-Cys]-Thr-NH 2 -DLys(Dop5)-Lys-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-Val-Cys] -Thr- NH 2 Dop6-Lys(Dop6)-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop7-Lys(Dop7)-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop8-Lys(Dop8)-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop9-Lys(Dop9)-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop 1 0-Lys(Dop 1 0)-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop] 11-Lys(Dopl 11)-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 DoplI2-Lys(Dopl12)-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Tin-NH 2 DoplI3-Lys(Dopl13)-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop6-Lys(Dop6)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys)-Thr-NH 2 Dop7-Lys(Dop7)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop8-Lys(Dop8)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Tin-NH 2 Dop9-Lys(Dop9)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Tin-NH 2 Dop IO-Lys(Dop IO)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Tin-NH 2 Dopl 11-Lys(Dopl 11)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 DoplI2-Lys(Dopl12)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Tin-NH 2 or Dopl13-Lys(Dopl13)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]- Tin-NH- 2 or a pharmaceutically acceptable salt thereof, wherein said therapeutically effective amount is the amount effective to treat prolactinemia in said patient. H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 00 146 The method of claim 4, wherein said chimeric analog comprises a agonist and a dopamine receptor agonist. 6. The method of claim 5, wherein said chimeric analog further comprises a SSTR- 2 agonist. 7. A method of treating portal hypertension in a subject in need thereof, wherein 00 said method comprises administering to said subject a therapeutically effective amount of a chimeric analog, wherein said chimeric analog comprises a compound according to the formula of: Formula (111), (VI) (VII), (VIII), or as set forth herein; or a pharmaceutically acceptable salt thereof; a compound selected from: Dop2-DPhe-Doc-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys- Val-Cys]-Thr-NH 2 Ac-Lys(Dop2)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Ac-DLys(Dop2)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-Lys(Ac)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DLys(Ac)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop3-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop3-Aepa-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop4-Aepa-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop6-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop7-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop8-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop9-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop IO-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dopl I-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 DoplI2-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop13 -DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 00 147 2 Dop6-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, Dop7-cycloI[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, Dop8-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop9-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, Dop 1 0-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dopl 1-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dopl12-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 00 DoplI3-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, Dop5-D2Nal-cyclo[Cys-Tyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 Dop6-D2NaI-cyclo[Cys-Tyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 Dop7-D2Na1-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH2, Dop8-D2NaI-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop9-D2NaI-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 DopI 0-D2NaI-cyclo[Cys-Tyr-DTrp-Lys-Va-Cys]-Thr-NH 2 Dop 11 -D2NaI-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop 1 2-D2Na1-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]l-Thr-NH2, Dop 1 3-D2Na1-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 -cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH2, Dop6-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop7-cyclo[Cys-Tyr-DTrp-Lys-Val-CysI-Thr-NH2, Dop8-cyclo[Cys-Tyr-DTrp-Lys-Va-Cys]-Thr-NH2, Dop9-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH2, Dop I 0-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dopl 1-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH2, DoplI2-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop13 -cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-oI, Dop6-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop7-DPhe-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-oI, Dop8-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop9-DPhe-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-oI, H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 00 148 Dop I 0-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dopl 11-DPhe-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dopl12-DPhe-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-oI, Dop 13 -DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-oI, Dop6-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-oI, Dop7-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop8-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, 00 Dp-yl[y-h-~pLsTrCs-h-l Dop9I -cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dopl I -cyclollCys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop 11 -cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop 1 2-cyclo[Cys-Phe-DTrp-Lys-Thr-CysI-Thr-ol, Dop5-13 -cyclo[Cys-e-DTrp-Lys-Thr-Cys]-r-l N2 Dop5 -DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop6-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Na-NH 2 Dop7-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2NaI-NH 2 Dop8-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop9I -DPhe-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dopl I 0-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop 11 -DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop I 2-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Na-NH 2 Dop5I3Dh-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2NaI-NH 2 [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop6-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop7-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop8-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop9I -cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-N H 2 Dop I I0-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop 11 -cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop I 2-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys]-2Na-NH 2 Dop I 3D-cyclo [Cys- Tyr-DTrp-Lys-Thr-Cys]-l-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 00 149 Dop2-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop 1 -Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop2-Aepa-DPhe-cyclolCys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop3 -Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop4-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop3 -DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop4-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 00 Dp-~eccoCs3~rDr-y-h-y]TrN2 Dop6-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-ThrNH 2 Dop7-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop8-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH2, Dop9I -DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 DopI 1 -DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 15Dopl11-DPhe-cyclo[Cys-3 lTyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 DoplI -DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop3 Dh-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop3 -cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop4-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 20Dop5 -cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop6-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop7-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop8-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop9-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 I 0-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dopl11-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dopl1 -cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop 13 -C-cyclo [DCys-3 Palr-DTrp-Lys-rCys] -ThrH 2 y-NH2 Dop21-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys]-Thr(BzI)-Tyr-NH 2 30Dop2-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop3 -Caeg-cyclo[DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop4I-A-Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(Bzl)-Tyr-N H 2 H:\MaraR\Keep\Speci\P64463-div-SPECI .doc 13/02/08 00 150 Dop2-Aepa-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys]-Thr(Bzl)-Tyr-NH 2 Dop3-Aepa-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop4-Aepa-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(BzI)-Tyr-NH 2 -Caeg-cyclo[DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop6-Caeg-cyclo [DCys-3PaI-DTrp-Lys-DCys] -Thr(BzI)-Tyr-NH 2 Dop7-Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop8 -Caeg-cyclo [DCys- 3PalI-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-N H2, Dop9-Caeg-cyclo [DCys- 3 Pal-DTrp- Lys- DCys] -Thr(Bzl)-Tyr-NH 2 00 ol -agccoDy-PlDr-y- ys-h(z)TrN2 D0 -agcco[~s3PID~pLsDy]-h(z)TrN 2 DopI 1-Caeg-cyclo[DCys-3PaI-DTrp-Lys-DCys]-Thr(Bz)-Tyr-NH2, Dop I 2-Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(BzI)-Tyr-NH 2 Dopl13-Caeg-cyclo[DCys-3Pal-DTrp-Lys-DCys]-Thr(Bz)-Tyr-NH2, Dop I -Caeg-cyclo [DCys- Phe-DTrp- Lys- DCys] -Ser(Bz)-Tyr-NH 2 Dop2-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dop3-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-NH2, Dop4-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-NH2, DoplI-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dop2-Aepa-Caeg-cyclollDCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dop3 -Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dop4-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 -Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-NH2, Dop6-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-NH 2 Dop7-Caeg-cyclollDCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr-NH 2 Dop8-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr-NH 2 Dop9-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr-NH 2 DopI1O-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-NH 2 Dop I11 -Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-NH2, Dopl12-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-NH 2 Dop13 -Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-SerBzl)-Tyr-NH 2 Dop5-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH 2 Dop6-cycloI[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH 2 Dop7-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI .doc 13/02/08 00 151 Dop8-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop9-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop I O-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop 1-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop 1 2-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop 1 3-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 No Dop5-DPhe-cyclollCys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 0o6Dh-yl CsPe(-eDr-y-h-y]TrN2 00 Dop7-DPhe-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH2, 010 Dop7-DPhe-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH2, Dop9-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop I -DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop 11 -DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop I I2-DPhe-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dopl 13-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop5 I3Dh-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys -Thr-NH 2 Dop6-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop7-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop8-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop9-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop Ip-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Ti-NH 2 Dop 11 -cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop I 2-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH2, Dopl 13-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Tin-NH 2 Dp-LDop3clop2)s-cyco y-TyrDTrp-Lys-Ab-Cys] -Tn-NH 2 Dop2-Lys(Dop2)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-Lys(Dop2)D-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Tn-NH 2 Dop2-Lys(Dop2)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Ti-NH 2 Dop2-Lys(Dop2)-D~yrey-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 ii:\Mara1R\Keep\Speci\P64463-div-SPECI.doc 13/02/08 00 152 Dop2-DLys(Dop2)-Lys-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 Dop2-DLys(Dop2)-DTyr-DTyr-cyclolCys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop I -Lys(Dop 1 )-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop I -Lys(Dop 1 )-Aepa-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop 1 -Lys(Dop 1 )-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop 1 -Lys(Dop 1 )-Lys-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 00 Dop I -Lys(Dop I )-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop I -DLys(Dop 1 )-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop I -DLys(Dop I)-Aepa-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop I -DLys(DoplI)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-N H 2 Dop 1 -DLys(DoplI)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop I -DLys(DoplI)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop I -Lys(Dopl1)-D2Nal-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop I -Lys(Dopl1)-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop 1 -Lys(Dopl1)-Lys-DTyr-DTyr-cyclo[~Cys-Tyr-DTrp-Lys-VaI-Cys] -Thr- NH 2 Dop 1 -Lys(DoplI)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop I -Lys(Dopl1)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop 1 -Lys(DoplI)-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop I -Lys(Dopl1)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2NaI- NH 2 Dop I -Lys(Dopl1)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2NaI -NH 2 Dop 1 -Lys(Dopl1)-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop 1 -Lys(Dopl1)-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-oI, Dop 1 -Lys(Dop I )-Lys-DTyr-DTyr-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-oI, Dop 1 -Lys(Dop I )-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-CysI-Thr-ol, Dop I -Lys(Dop2)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Va-Cys]-Trp-NH2, DoplI-Lys(Dop2)- cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Tmp-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 153 00 Dop 1 -Lys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Trp- NH 2 Dop 1 -Lys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Trp-NH 2 Dop2-Lys(Dop2)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-Aepa-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-Lys-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 00 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, Dop2-Lys(Dop2)-Aepa-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop2-DLys(Dop2)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, Dop2-DLys(Dop2)-Aepa-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-DLys(Dop2)-Lys-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 Dop2-DLys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-Aepa-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop2-Lys(Dop2)-D2Na1-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr- NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH2, Dop2-Lys(Dop2)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Na-NH 2 Dop2-Lys(Dop2)-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop2-Lys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2NaI- NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop2-Lys(Dop2)-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-oI, Dop2-Lys(Dop2)-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop2-Lys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, H\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 00 154 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop2-Lys(Dop2)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 Dop2-Lys(Dop2)- cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH2, Dop2-Lys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Trp- NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Trp-NH 2 NoDop3 -Lys(Dop3)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 0 00 Dop3 -Lys(Dop3)-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop3 -Lys(Dop3)-Lys-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 Dop3 -Lys(Dop3 )-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop3 -DLys(Dop3)-DPhe-cyclollCys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop3 -DLys(Dop3 )-Aepa-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, Dop3 -DLys(Dop3 )-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop3 -DLys(Dop3)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop3-DLys(Dop3 )-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop3 -Lys(Dop3)-D2Na1-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys]-Thr-NH 2 Dop3 -Lys(Dop3)-cyclo[Cys-Tyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 Dop3 -Lys(Dop3)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr- NH 2 Dop3 -Lys(Dop3)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]l-Thr-NH2, Dop3-.Lys(Dop3)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop3 -Lys(Dop3)-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH2, Dop3-Lys(Dop3)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal- NH 2 Dop3 -Lys(Dop3 )-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop3 -Lys(Dop3)-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop3 -Lys(Dop3 )-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-oI, Dop3 -Lys(Dop3)-Lys-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-oI, Dop3 -Lys(Dop3)-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, H:\MaraR\Keep\Speci\P64463div-SPECIdoc 13/02/08 00 155 Do3-y(o3-0ecco[y-TrDr-y-a-y]TpN 2 Dop3 -Lys(Dop3)-D cyclo [Cys-Tyr-DTrp-Lys-Va-Cys -Trp-NH 2 Dop3 -Lys(Dop3)-Ly- -~rcyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Trp- NH 2 Dop3 .Lys(Dop3)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Va-Cys] -Trp-NH 2 Dop4-Lys(Dop4)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Tim-NH 2 Dop4-Lys(Dop4)-Aepa-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop4-Lys(Dop4)-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 00 Dop4-Lys(Dop4)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 Dop4-Lys(Dop4)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-DLys(Dop4)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, Dop4-DLys(Dop4)-Aepa-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-DLys(Dop4)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-DLys(Dop4)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop4-DLys(Dop4)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-L ys-Abu-Cys] -Thr-NH 2 Dop4-Lys(Dop4)-D2Nal-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop4-Lys(Dop4)-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop4-Lys(Dop4)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys]-Thr- NH 2 Dop4-Lys(Dop4)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 Dop4-Lys(Dop4)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Na-NH2, Dop4-Lys(Dop4)-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH2, Dop4-Lys(Dop4)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal- NH 2 Dop4-Lys(Dop4)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop4-Lys(Dop4)-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop4-Lys(Dop4)-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop4-Lys(Dop4)-Lys-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-oI, Dop4-Lys(Dop4)-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop4-Lys(Dop4)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH2, H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 00 156 Do4LsDp) yl[y-yrDr-y-a-y]TpN2 Dop4-Lys(Dop4)-Ly- -~rcyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Trp- NH 2 Dop4-Lys(Dop4)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH2, Dop5 -Lys(Dop5)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 -Lys(Dop5)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr- 00 NH 2 Dop5-Lys(Dop5)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-N H 2 -DLys(Dop5)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 Dop5 -DLys(Dop5)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, -Lys(Dop5)-D2Na1-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 -Lys(Dop5)-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 [Cys-Tyr-DTrp-Lys-VaI-Cys] -Thr- NH 2 Dop5 -Lys(Dop5)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 -Lys(Dop5)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Na-NH 2 [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal- NH 2 Dop5 -Lys(Dop5)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2NaI-NH 2 [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, [Cys-Phe-DTrp-Lys-Thr-CysJ-Thr-ol, [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, -Lys(Dop5)-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop5 -Lys(Dop5)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH 2 cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI .doc 13/02/08 00 157 [Cys-Tyr-DTrp-Lys-VaI-Cys] -Trp- NH 2 [Cys-Tyr-DTrp-Lys-VaI-Cys] -Trp-NH 2 Dop6-Lys(Dop6)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop6-Lys(Dop6)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop6-Lys(Dop6)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Tin- No NH 2 0 00 Dop6-DLys(Dop6)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop6-DLys(Dop6)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop6-DLys(Dop6)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 Dop6-DLys(Dop6)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop6-Lys(Dop6)-D2Na1-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 Dop6-Lys(Dop6)-cyclo [Cys-Tyr-DTrp-Lys-Va1-Cys] -Thr-NH 2 Dop6-Lys(Dop6)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr- NH 2 Dop6-Lys(Dop6)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Va1-Cys] -Thr-NH 2 Dop6-Lys(Dop6)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop6-Lys(Dop6)-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop6-Lys(Dop6)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal- NH 2 Dop6-Lys(Dop6)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Na-NH 2 Dop6-Lys(Dop6)-DPhe-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-o, Dop6-Lys(Dop6)-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop6-Lys(Dop6)-Lys-DTyr-DTyr-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-oI, Dop6-Lys(Dop6)-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop6-Lys(Dop6)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH2, Dop6-Lys(Dop6)- cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Trp-NH 2 Dop6-Lys(Dop6)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Trp- NH 2 Dop6-Lys(Dop6)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Tmp-NH 2 H:\MaraR\Keep\speci\P64463-div-SPECI.doc 13/02/08 00 158 Dop7-Lys(Dop7)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop7-Lys(Dop7)-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, Dop7-DLys(Dop7)-DPhe-cyclolCys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop7-DLys(Dop7)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH 2 Dop7-Lys(Dop7)-D2Nal-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop7-Lys(Dop7)-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop7-Lys(Dop7)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop7-Lys(Dop7)-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 00 Dop7-Lys(Dop7)-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-oI, Dop7-Lys(Dop7)-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-oI, Dop7-Lys(Dop7)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH 2 Dop7-Lys(Dop7)- cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 Dop8-Lys(Dop8)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop8-Lys(Dop8)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop8-DLys(Dop8)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop8-DLys(Dop8)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop8-Lys(Dop8)-D2Na1-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop8-Lys(Dop8)-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop8-Lys(Dop8)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys]-2Na-NH2, Dop8-Lys(Dop8)-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop8-Lys(Dop8)-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop8-Lys(Dop8)-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop8-Lys(Dop8)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH 2 Dop8-Lys(Dop8)- cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Tmp-NH 2 Dop9-Lys(Dop9)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop9-Lys(Dop9)-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop9-DLys(Dop9)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop9-DLys(Dop9)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop9-Lys(Dop9)-D2Na1-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop9-Lys(Dop9)-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop9-Lys(Dop9)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop9-Lys(Dop9)-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 H:\MaraR\Keep\speci\P64463-div-SPECI .doc 13/02/08 00 -159 Dop9-Lys(Dop9)-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop9-Lys(Dop9)-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop9-Lys(Dop9)-DPhe-cyclolCys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 Dop9-Lys(Dop9)- cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys]-Trp-NH 2 DopI1 -Lys(DoplI )-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, DopI1O-Lys(DoplI )-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, NoDopI1 -DLys(DoplI )-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 DopI1 -DLys(DoplI )-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 00 Dop 1 -Lys(Dopl1O)-D2Na1-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 DopI1 -Lys(DoplI )-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 DopI1 -Lys(DoplI )-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Na-NH 2 DopI1O-Lys(DoplI )-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop 1O-Lys(Dopl1O)-DPhe-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop I -Lys(DoplI )-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-oI, DopI1 -Lys(Dopl1 )-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 DopI1 -Lys(Dop 10)- cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 Dop I11 -Lys(Dop Ii )-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, Dop 11 -Lys(Dopl II)-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop 11 -DLys(Dopl 11)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop I -DLys(Dopl 11)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop I11 -Lys(Dop 11 )-D2Na1-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop 11 -Lys(Dopl 11)-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dopl 11-Lys(Dopl 11)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dopi I -Lys(Dopl 1)-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH2, Dopl 11-Lys(Dopl 11)-DPhe-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop I11 -Lys(Dop I1 )-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dopl I-Lys(Dopl 11)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH 2 Dopi I -Lys(DopI cyclo[Cys-Tyr-DTrp-Lys-Val-CysJ-Trp-NH2, Dopl12-Lys(Dopl12)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 DoplI2-Lys(DoplI2)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thir-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 00 160 Dop I 2-DLys(Dop 1 2)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, Dop 1 2-DLys(Dop I 2)-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop 1 2-Lys(Dop I 2)-D2Na1-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 Dop I 2-Lys(Dop 1 2)-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 Dop 1 2-Lys(Dop 1 2)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop I 2-Lys(Dop 1 2)-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 No Dop 1 2-Lys(Dop I 2)-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-oI, Dop 1 2-Lys(Dop I 2)-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-oI, 00 Dop 1 2-Lys(Dop 1 2)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 DoplI2-Lys(Dop 12)- cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH 2 Dop13 -Lys(DoplI3)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop13 -Lys(Dop13 )-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop 13-DLys(Dopl1 )-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 DoplI3-DLys(Dop13 )-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop13 -Lys(Dopl13)-D2NaI-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 DoplI3-Lys(Dopl13)-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop13 -Lys(Dop13 )-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH2, Dop13 -Lys(DoplI3)-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop13 -Lys(DoplI3)-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop13 -Lys(Dopl13)-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop13 -Lys(Dop I3)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH2, Dop13 -Lys(Dop 13)- cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Trp-NH 2 Dop 1 -Lys(Dop 1 )-Caeg-cyc lo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop1-Lys(Dop1)-Caeg-cyclojIDCys-Phe-DTrp-Lys-DCys]-Ser(Bz)-Tyr-NH2, Dop 1 -DLys(Dop I )-Caeg-cyclo [DCys-3 Pal- DTrp- Lys- DCys] -Thr(BzI)-Tyr- NH 2 Dopl1-DLys(Dopl1)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr-NH 2 Dop 1 -Lys(Dop 1 )-Lys-Caeg-cyclo [DCys-3 PalI-DTrp-Lys-DCys] -Thr(BzI)-Tyr- NH 2 Dopl1-Lys(DoplI)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr- NH 2 H:\Mar&R\Keep\Speci\P64463div-SPECI.doc 13/02/08 00 161 Dop 1 -DLys(DoplI)-Lys-Caeg-cyclo[DCys-3 Pa1-DTrp-Lys-DCys]-Thr(Bz1)-Tyr- NH 2 Dop I -DLys(Dop 1 )-Lys-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr- NH 2 Dop 1 -Lys(Dop 1 )-Aepa-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(BzI)-Tyr- NH 2 Dop I -Lys(Dop 1 )-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr- NH 2 00 Dop 1 -DLys(Dop 1 )-Aepa-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(BzI)- Tyr-NH 2 Dop 1 -DLys(Dop I )-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bz)- Tyr-NH 2 Dop I -Lys(Dop I )-Lys-Aepa-Caeg-cyc lo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(BzI)- Tyr-NH 2 Dop I -Lys(Dop I)-Lys-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)- Tyr-NH 2 Dop I -DLys(Dop 1 )-Lys-Aepa-Caeg-cyc lo [DCys- 3 Pal-DTrp- Lys- DCys] Thr(BzI)-Tyr-NH 2 Dop 1 -D Lys(Dop I )-Lys-Aepa-Caeg-cyclo [DCys-Phe-DTrp- Lys-DCys] Ser(Bzl)-Tyr-NH 2 Dop2-Lys(Dop2)-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop2-Lys(Dop2)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr-NH 2 Dop2-DLys(Dop2)-Caeg-cyclo [DCys-3 Pal- DTrp- Lys-DCys] -Thr(Bzl)-Tyr- NH 2 Dop2-DLys(Dop2)-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bz)-Tyr-NH2, Dop2- Lys(Dop2)-Lys-Caeg-cyclo [DCys-3 PalI-DTrp-Lys-DCys) -Thr(Bzl)-Tyr- NH 2 Dop2-Lys(Dop2)-Lys-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bz)-Tyr- NH 2 Dop2-DLys(Dop2)-Lys-Caeg-cyc lo [DCys-3 Pal- DTrp-Lys-DCys] -Thr(Bzl)-Tyr- NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 00 162 Dop2-DLys(Dop2)-Lys-Caeg-cycloIIDCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr- NH 2 Dop2-Lys(Dop2)-Aepa-Caeg-cyclo[DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr- NH 2 59 Dop2-Lys(Dop2)-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr- NH 2 Dop2-DLys(Dop2)-Aepa-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys]-Thr(Bzl)- Tyr-NH 2 00 Dop2-DLys(Dop2)-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)- Tyr-NH 2 Dop2-Lys(Dop2)-Lys-Aepa-Caeg-cyclo [DCys-3 PalI-DTrp- Lys-DCys] -Thr(Bzl)- Tyr-NH 2 Dop2-Lys(Dop2)-Lys-Aepa-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(BzI)- Tyr-NH 2 Dop2-DLys(Dop2)-Lys-Aepa-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys]- Thr(Bzl)-Tyr-NH 2 Dop2-DLys(Dop2)-Lys-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] Ser(Bzl)-Tyr-NH 2 Dop3 -Lys(Dop3)-Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(Bz1)-Tyr-NH2, Dop3-Lys(Dop3)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bz1)-Tyr-NH2, Dop3 -Lys(Dop3)- Lys-Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(Bzl)-Tyr- NH 2 Dop3-Lys(Dop3)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCysJ-Ser(Bzl)-Tyr- NH 2 Dop3 -Lys(Dop3 )-Aepa-Caeg-cyclo [DCys-3 Pal -DTrp- Lys-DCys] -Thr(Bzl)-Tyr- NH 2 Dop3 -Lys(Dop3)-Aepa-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr- NH 2 Dop3 -D Lys(Dop3)-Caeg-cyclo [DCys-3 Pal- DTrp-Lys- DCys] -Thr(BzI)-Tyr- NH 2 Dop3 -DLys(Dop3)-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI .doc 13/02/08 00 163 Dop3 -DLys(Dop3 )-Lys-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(BzI)-Tyr- NH- 2 Dop3 -DLys(Dop3)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr- NH 2 Dop3 -DLys(Dop3 )-Aepa-Caeg-cyclo[DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)- Tyr-NH 2 Dop3-DLys(Dop3)-Aepa-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bz)- Tyr-NH 2 00 Dp-y(o4-agccoDy-PlDr-y-~s-h(z)TrN2 10Dop4-Lys(Dop4)-Caeg-cyclo [DCys-3Pa-DTrp-Lys-DCys] -Tr(Bz)-Tyr-NH 2 Dop4-Lys(Dop4)-LCaeg-cyclo [DCys-P-DTrp-Lys-DCys]-(13z1)-Tyr-2 NH 2 Dop4-Lys(Dop4)-Lys-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr- NH 2 Dop4-Lys(Dop4)-Aepa-Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(Bzl)-Tyr- NH1 2 Dop4-Lys(Dop4)-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr- NH4 2 Dop4-Lys(Dop4)-Lys-Aepa-Caeg-cyclo [DCys-3 PalI-DTrp- Lys-DCys] -Thr(Bzl)- Tyr-NH 2 Dop4-Lys(Dop4)-Lys-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)- Tyr-N14 2 Dop4-D Lys(Dop4)-Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(Bzl)-Tyr- NH 2 Dop4-DLys(Dop4)-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dop4-D Lys(Dop4)-Lys-Caeg-cyclo [DCys-3 Pal- DTrp-Lys-DCys] -Thr(Bzl)-Tyr- NH 2 Dop4-DLys(Dop4)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(BzI)-Tyr- NH 2 Dop4-DLys(Dop4)-Aepa-Caeg-cyclo [DCys-3Pal-DTrp-Lys-DCys]-Thr(Bzl)- Tyr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 00 164 Dop4-DLys(Dop4)-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)- Tyr-NH 2 Dop4-DLys(Dop4)-Lys-Aepa-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] Thr(Bzl)-Tyr-NH 2 Dop4-DLys(Dop4)-Lys-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys)- Ser(Bzl)-Tyr-NH 2 Dop5-Lys(Dop5)-Caeg-cyclo[DCys-3Pal-DTrp-Lys-DCys]-Thr(Bzl)-Tyr-NH2, -Lys(Dop5)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 00 ~Dop5 -D Lys(Dop5 )-Caeg-cyclo [DCys-3 PalI-DTrp-Lys-DCys] -Thr(BzI)-Tyr- NH 2 -DLys(Dop5)-Caeg-cycl o [DCys-Phe-DTrp- Lys- DCys] -Ser(BzI)-Tyr-NH 2 -Lys(Dop5)-Lys-Caeg-cyclo [DCys-3 PalI-DTrp-Lys-DCys] -Thr(Bzl)-Tyr- NH 2 -Lys(Dop5)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr- NH 2 Dop5-DLys(Dop5)-Lys-Caeg-cyclo[DCys-3 Pal-DTrp-Lys-DCys] -Thr(BzI)-Tyr- NH 2 [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr- NH 2 Dop6-Lys(Dop6)-Caeg-cyclo [DCys-3PaI-DTrp-Lys-DCys]-Thr(Bzl)-Tyr-NH2, Dop6-Lys(Dop6)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-NH2, Dop6-DLys(Dop6)-Caeg-cycl o[DCys-3 Pal- DTrp-Lys-DCys] -Thr(Bzl)-Tyr- NH 2 Dop6-DLys(Dop6)-Caeg-cyclollDCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dop6-Lys(Dop6)-Lys-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys]-Thr(BzI)-Tyr- NH 2 Dop6-Lys(Dop6)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr- NH- 2 Dop6-DLys(Dop6)-Lys-Caeg-cyclo [DCys-3 PalI-DTrp-Lys-DCys] -Thr(Bzl)-Tyr- NH 2 Dop6-DLys(Dop6)-Lys-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr- NH 2 H: \MaraR\Keep\Speci\P64463-div-SPECI .doc 13/02/08 00 165 Dy-PlDr-y-~s-h(z)TrN 2 Dop7-Lys(Dop7)-Caeg-cyclo [DCys-3Pe-DTrp-Lys-DCys]-er(Bz)-Tyr-NH 2 Dop7-Lys(Dop7)L-Caeg-cyclo[DCys-Pl-DTrp-Lys-DCys]-hr(Bzl)-Tyr-2 NH 2 Dop7-Lys(Dop7)-Lys-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr- NH 2 Dop8 -Lys(Dop8)-Caeg-cyclo [DCys-3 PalI-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-N H 2 Dop8-Lys(Dop8)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 00 Dop8-Lys(Dop8)-Lys-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(BzI)-Tyr- NH 2 Dop8-Lys(Dop8)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr- NH 2 Dop9- Lys(Dop9)-Caeg-cyclo [DCys-3 Pal-DTrp- Lys- DC ys] -Thr(BzI)-Tyr-N H 2 Dop9-Lys(Dop9)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]l-Ser(Bzl)-Tyr-NH 2 Dop9-Lys(Dop9)-Lys-Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(Bzl)-Tyr- NH 2 Dop9-Lys(Dop9)-Lys-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]l-Ser(Bz)-Tyr- NH 2 Dop I O-Lys(Dopl I )-Caeg-cyclo [DCys-3 Pat- DTrp-Lys-DCys] -Thr(Bzl)-Tyr- NH 2 Dop 1 O-Lys(Dop 1 O)-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr- NH 2 Dop I O-Lys(Dopl I )-Lys-Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(Bzl)- Tyr-NH 2 DopI O-Lys(DoplIO)-Lys-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr- NH 2 Dopl 11-Lys(Dopl I)-Caeg-cyclo [DCys-3 Pal- DTrp-Lys-DCys] -Thr(Bzl)-Tyr- NH 2 DopI I-Lys(Dopl 11)-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr- NH 2 DopI 1 -Lys(Dopl 11)-Lys-Caeg-cycl o [DCys-3 PalI-DTrp- Lys-DCys] -Thr(BzI)- Tyr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 00 166 Dopl 11-Lys(Dopl 11)-Lys-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr- NH 2 Dop 1 2- Lys(Dop I 2)-Caeg-cyclo [DCys-3 PalI-DTrp-Lys-DCys] -Thr(Bzl)-Tyr- NH 2 Dopl12-Lys(Dopl12)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr- NH 2 Dop 12- Lys(DoplI 2)-Lys-Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(Bz)- Tyr-NH 2 00DoplI2-Lys(DoplI2)-Lys-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(BzI)-Tyr- NH 2 (NH2 DopI 13-Lys(Dop I 3)-Caeg-cyclo [DCys-3Pa-DTrp-Lys-DCys]-Tr(Bzl)-Tyr- NH 2 DopI 3-Lys(Dopl 3)-LCaeg-cyco [DCys-PlDTrp-Lys-DCys -r(Bz)-r TNH 2 3-Lys(Dopl 3)-Lys-Caeg-cyclo[DCys-3PaI-DTrp-Lys-DCys]-Thr(BzI)-Tr TNH 2 DopI -Lys(Dopl)-LCe-cyclo[DCys -Phe-DTrp-Lys-DeCys]-SerBz)-yr Dop I -Lys(Dop)-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH2, DoplI-Lys(Dop)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 DoplI -Lys(Dop)-cyclo [Cys-Phe-Ph-eDTrp-Lys-Thr-he-Cys]-NH 2 Dop 1 -DLys(Dopl1)-Dh-cycloCys-Phe-(§N-Me)DTrp-Lys-Thr-Cys] -in-NH 2 25Dop2I-Lys(Dop21)-cyclo[Cys-Phe-(N-MDTrp-Lys-Thrh-Cys] NH 2 Dop2I-Lys(Dop)D-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -T-NH 2 Dop2-Lys(Dop2)-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH2, Dop2-Lys(Dop2)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Tn-NH 2 Dop2-Lys(Dop2)-cyclo [Cys-Phe-Ph-eDTrp-Lys-Thr-eCys]-rNH 2 30Dop2-DLys(Dop2)-D-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-cyclo [Cys-Phe-(N-MDTrp-Lys-Thrh-Cys] -NH 2 Dop2-Lys(Dop)D-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -T-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 00 167 Do3-y(o3-yl CsPe(NM)0pLsTrCs TrN 2 Dop4-Lys(Dop4)-cyclo [Cys-Phe-Ph-eDTrp-Lys-Thrh-Cys]T-NH 2 Dop4-Lys(Dop4)-D-cyclo [Cys-Phe-N-DTrp-Lys-Thr -Cys]h-NH 2 Dop4-Lys(Dop4)-Dh-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH2, Dop4-Lys(Dop5)-cyclo[Cys-Phe-Ph-e-DTrp-Lys-Thrh-Cys]-T -NH 2 5Dop5-Lys(Dop5)-D-cyclo [Cys-Phe-N-DTrp-Lys-Thr -Cys]h-NH 2 [Cysh-Phe-NeDTrp-Lys-Thr-Cys]-hr-, 2 [Cys-Phe-N-DTrp-Lys-Thr -Cys] h-NH 2 005Dy(o5-~ecyl[y-h-NM)~p-y-h-y]TrN2 00 Dop5-Lys(Dop5)-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop5-DLys(Dop5 )-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop6-Lys(Dop6)-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop6-Lys(Dop6)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop6-DLys(Dop6)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH2, Dop6-DLys(Dop6)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop6-Lys(Dop6)-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop6-DLys(Dop6)-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop7-Lys(Dop7)-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH2, Dop7-Lys(Dop7)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop7-Lys(Dop7)-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop8-Lys(Dop8)-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH2, Dop8-Lys(Dop8)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop9-Lys(Dop9)-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop9-Lys(Dop9)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop I O-Lys(Dop 1 0)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop 1 O-Lys(Dopl I )-DPhe-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop 11 -Lys(Dop 11 )-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH2, Dopl 11-Lys(Dopl 11)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dopi 2-Lys(DoplI2)-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH2, Dopl12-Lys(Dopl12)-DPhe-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop13 -Lys(Dopl13)-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dopi 3-Lys(Dopl 3)-DPhe-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dopl1-DPhe-cyclo[Cys-3 ITyr(Dopl1)-DTrp-Lys-VaI-Cys] -Thr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI .doc 13/02/08 00 168 Doi-0eDcDh-yl[y-IyrDp)Dr-y-a-y]TrN2 Dop 1 -D~ys(Dop c-DPhe-cyclo [Cys-3 ITyrDp-DTrp-Lys-r-Cys] -Thr-NH 2 Dop I -DLys(Dop 1 )A-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop 1 -Lys(Dop )-eyr-Dyr-cyclo[Cys-3 Tyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dopi -Lys(Dop l)-D~yhe~y-cycloCys-3lTyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop I -Lys(Dopl1)-A-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 00Dop I -Lys(Dop )eah-cyclo [Cys-3 Tyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 0 Dop 1 -Lys(Dop )-cyclo [Cys-3 Tyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 I -Lys(Dop l )-yDrDr-cyclo[Cys-3ITyr-DTrp-Lys-Thr-Cys] -Thr- NH 2 Dop 1 -DLys(DoplI)-DTyr-DTyr-cyclo [Cys-31ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop I -DLys(DoplI)-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr- NH 2 Dop 1 -DLys(Dop 1 )-DPhe-cyclo [Cys-3 lTyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop 1 -DLys(Dop 1 )-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 Dop 1 -Lys(DoplI)-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop 1 -Lys(Dopl1)-DPhe-cyclo [Cys-31ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop 1 -Lys(Dop I )-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop 1 -DLys(Dop 1 )-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop 1 -Lys(Dop 1 )-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-N H 2 Dop 1 -Lys(Dop 1 )-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Tbr- NH 2 Dop 1 -DLys(Dop 1 )-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop 1 -DLys(Dop I )-Lys- DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dopi1 -DLys(Dopl )-DPhe-cyclo[Cys-3Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop I -DLy s(Dop 1 )-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Gys] -Thr-N H 2 H:\MaraR\Kcep\Speci\P64463-div-SPECI.doc 13/02/08 00 169 Do0 LsDpI)Dy-~rcco[y- ~rDr-y-a-y]TrN 2 Dop 1 -Lys(DoplI)-D~yrDey-cyclo[Cys-31Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop I -Lys(DoplI)-A-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop I -Lys(Dop)Aeah-cyclo [Cys-31Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 I -Lys(Dop)-cyclo [Cys-3 Tyr-DTrp-Lys-Va-Cys] -Thr-NH 2 Dop 1 -Lys(DoplI)LyDrDy-cyclo [Cys-3 ITyr-DTrp-Lys-VaI-Cys]-Thr- NH 2 ,y(ol-ysDy-~rcco[y-ly-~pLy-a-y]Tr 002 ooDop 1 -DLys(DoplI)-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr-NH2, Dop 1 -DLys(Dopl1)-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-VaI-Cys]-Thr- NH 2 Dop2-DPhe-cyclo [Cys-3 ITyr(Dop2)-DTrp-Lys-VaI-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-Aepa-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr- NH 2 Dop2-Lys(Dop2)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-Aepa-DPhe-cyclolCys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-Aepa-DPhe-cyclo[Cys-3 lTyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop2-DLys(Dop2)-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-CysI-Thr-NH 2 Dop2-Lys(Dop2)-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-Lys-DTyr-DTyr-cyclolCys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr- NH 2 Dop2-DLys(Dop2)-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop2-DLys(Dop2)-Aepa-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] Thr-NH 2 Dop2-DLys(Dop2)-Lys-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr- NH 2 Dop2-DLys(Dop2)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 )4\MaraJ\Keep\Speci\P64463-div-SPECIdoc 13/02/08 00 170 Dop2-DLys(Dop2)-Aepa-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 s Dop2-Lys(Dop2)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 IND Dop2-DLys(Dop2)-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 0o2LsDp)cco[y- ~rDr-y-b-y]TrN 2 00 ~~Dop2-Lys(Dop2)Ly-rDr-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop2-DLys(Dop2)-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 Dop2-DLys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-3 lTyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 Dop2-DLys(Dop2)-DPhe-cyclo [Cys-3 lTyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-Aepa-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-cyclo [Cys-3 lTyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr- NH 2 Dop2-DLys(Dop2)-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-VaI-Cys]-Thr-NH 2 Dop2-DLys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys] -Thr- NH 2 Dop3-Lys(Dop3)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop4-Lys(Dop4)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop3 -Lys(Dop3)-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop4-Lys(Dop4)-Aepa-DPhe-cyclo[Cys-3 LTyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 -DLys(Dop5)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 H:\MaraR\Keep\Speci\P64463-diV-SPECI.doc 13/02/08 00 171 0o5LsDp)Dy-~rcco[y-3Iy-~pLsTrCs TrN 2 [Cys-3 Tyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 )D-cyclo [Cys-3 Tyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop5-Lys(Dop5)-cyclo [Cys-3 Tyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop5-Lys(Dop5)LyDrDr-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr- [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-, 0 00 Dop5-DLys(Dop5)-Lys-DTyr-DTyr-cyclo[Cys-3 lTyr-DTrp-Lys-Thr-Cys]-Thr- NH 2 )-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop5-Lys(Dop5)-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop5-Lys(Dop5)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop5-DLys(Dop5)-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys]-Thr-NH2, [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop5-DLys(Dop5)-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 Dop5-DLys(Dop5)-Lys-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 [Cys-3 ITyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 [Cys-3 ITyr-DTrp-Lys-VaI-Cys]-Thr-NH 2 Dop5-Lys(Dop5)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Val-Cys] -Thr-NH 2 [Cys-3 ITyr-DTrp-Lys-Val-Cys] -Thr-NH 2 [Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr-NH 2 [Cys-3 ITyr-DTrp-Lys-Val-Cys] -Thr- NH 2 Dop5-DLys(Dop5)-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-Val-Cys] -Thr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 172 00 Dop5-DLys(Dop5)-Lys-DTyr-DTyr-cyclolCys.3 ITyr-DTrp-Lys-Val-Cys] -Thr- NH 2 Dop6-Lys(Dop6)-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop7-Lys(Dop7)-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop8-Lys(Dop8)-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop9-Lys(Dop9)-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop 1 O-Lys(Dop 1 0)-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 DopI 11-Lys(DopI 11)-cyclollCys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 00 DoplI2-Lys(DoplI2)-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop I 3-Lys(Dop I 3)-cyclo[Cys-3ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop6-Lys(Dop6)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop7-Lys(Dop7)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop8-Lys(Dop8)-DPhe-cyclo [Cys-31ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop9-Lys(Dop9)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop I O-Lys(Dop I O)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 DopI 11-Lys(Dopl 11)-DPhe-cyclo [Cys-31ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 DoplI2-Lys(Dopl12)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 or Dop13 -Lys(Dopl13)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] Thr-NH- 2 or a pharmaceutically acceptable salt thereof; wherein said therapeutically effective amount is the amount effective to treat portal hypertension in said patient. 8. A method of treating gastrointestinal bleeding in a subject in need thereof, wherein said method comprises administering to said subject a therapeutically effective amount of a chimeric analog, wherein said chimeric analog comprises a compound according to the formula of: Formula (III), (VI) (VII), (VIII), or as set forth herein; or a pharmaceutically acceptable salt thereof-, a compound selected from: Dop2-DPhe-Doc-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Ac-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Ac-DLys(Dop2)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop2-Lys(Ac)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI doc 13/02/08 00 173 Dop2-DLys(Ac)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop3 -DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop3 -Aepa-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-Aepa-DPhe-cyclollCys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop6-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop7-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 00 Dop8-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop9.-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop I O-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop I11 -DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop 1 2-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop 1 3-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop5 -cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop6-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop7-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop8-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop9-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop 1 0-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop I1-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, Dop 1 2-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop 1 3-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 -D2Na1-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop6-D2NaI-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop7-D2Na1-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop8-D2Na1-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop9-D2Na1-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 Dop I O-D2Na1-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop I I -D2NaI-cyclo [Cys-Tyr-DTrp-Lys-Va1-Cys] -Thr-NH 2 Dop I 2-D2NaI-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dopl 13-D2NaI-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECIdoc 13/02/08 174 00 -cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop6-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop7-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 Dop8-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop9-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop 1 O-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop I1-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 Dop I 2-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 00 Dop 1 3-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop5-DPhe-cyclo [Cys-Phe-DTrp-Lys-Tbr-Cys] -Thr-ol, Dop6-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop7-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop8-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-oI, Dop9-DPhe-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop 1 O-DPhe-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-oI, Dop I1-DPhe-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop 1 2-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dopl 13-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, -Thr-oI, Dop6-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop7-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop8-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop9-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-oI, Dop I 0-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop I1I -cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-oI, Dopl12-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dopl 13-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, [Cys-Tyr-DTrp-Lys-Thr-Cys] -2NaI-NH 2 Dop6-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2NaI-NH 2 Dop7-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Na-NH 2 Dop8-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop9-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 00 175 00lODh-yl[CsTrDr-y-TrCs-NlN2 Dopl I O-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2NaI-NH 2 Dopl11-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dopl 1 -DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2NaI-NH 2 5Dop51 Dh-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys -2NaI-NH 2 Dop6-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop6-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop7-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2NaI-NH 2 00 Dop8-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 00 Dop9 -cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop 1 IO-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2NaI-NH 2 Dop 11 -cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop I 2-cyclo[Cys-Tyr-DTrp-Lys-Thr-CysI-2Nal-NH 2 Dop 13 -D-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys]-l-NH 2 15Dop21-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 15Dop21-A-DPhe-cyclo [Cys-31Tyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop21-Aepa-DPhe-cyclo[Cys-3ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop2-Aepa-DPhe-cyclolCys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop3 -Aepa-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 20Dop4-p-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop3 -DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop4-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop6-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop7-DPhe-cyclo [Cys-3 lTyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop8-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop9I -DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dopl 1 -DPhe-cyclo [Cys-3 lTyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dopl11-DPhe-cyclo [Cys-3 lTyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 -DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 ~Dop3-Dh-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop3 -cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPEcr.doc 13/02/08 00 176 [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop6-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop7-cyclo[Cys-3 LTyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop8-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop9-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop I 0-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 DopI 1-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dopl12-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 00Dop13 -cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dopl1-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop2-Caeg-cyclo[DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop3 -Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop4-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys]-Thr(Bzl)-Tyr-NH 2 Dop 1 -Aepa-Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop2-Aepa-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop3 -Aepa-Caeg-cyclo[DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop4-Aepa-Caeg-cyclo[DCys-3 Pal-DTrp-Lys-DCys] -Thr(BzI)-Tyr-NH 2 -Caeg-cyclo [DCys-3 PalI-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop6-Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop7-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(BzI)-Tyr-NH 2 Dop8-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(BzI)-Tyr-NH 2 Dop9-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop I 0-Caeg-cyclo[DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop 11 -Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(Bzl)-Tyr-N H2, DoplI2-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys]-Thr(Bzl)-Tyr-NH 2 Dopi 3-Caeg-cyclo[DCys-3Pal-DTrp-Lys-DCys]-Thr(Bzl)-Tyr-NH2, Dopl1-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr-NH 2 Dop2-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dop3 -Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-NH2, Dop4-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-NH 2 Dop I -Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr-NH 2 Dop2-Aepa-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 177 00 Dop3 -Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dop4-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 -Caeg-cyclo [DCys-Phe-DTrp- Lys- DCys] -Ser(Bzl)-Tyr-NH 2 Dop6-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dop7-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dop8-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-NH 2 Dop9-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-NH 2 Dop 1 O-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 00 Dop 11 -Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-NH 2 Dop I 2-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-NH 2 Dopl 13-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -SerBzl)-Tyr-NH 2 -cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop6-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop7-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH 2 Dop8-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop9-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop I 0-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH 2 Dop I11 -cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH 2 Dop 1 2-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH 2 Dop 1 3-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH 2 [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop6-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop7-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH2, Dop8-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop9-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-N H 2 Dop I O-DPhe-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop I11 -DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop 1 2-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]l-Thr-NH 2 Dop 1 3-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop5-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop6-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop7-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thir-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI .doc 13/02/08 178 00 Dop8-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop9-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop 1 O-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop I11 -cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop 1 2-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop I 3-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 0o2Dy(o2-yl CsTrDr-y-b-y]TrN 2 00 ~Dop2-Lys(Dop2)D-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 Dop2-DLys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop2-DLys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop I -Lys(Dop I )-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop 1 -Lys(DoplI)-Aepa-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop I -Lys(Dopl1)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop I -Lys(Dop 1 )-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 Dop I -Lys(DoplI)-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop I -DLys(Dop 1 )-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop I -DLys(Dop 1 )-Aepa-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop I -DLys(Dop I )-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop 1 -DLys(Dop 1 )-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop I -DLys(Dop 1 )-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop 1 -Lys(Dop 1 )-D2NaI-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop 1 -Lys(DoplI)-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop 1 -Lys(Dop 1 )-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr- NH 2 H:\MaraR\Keep\Speci\P64463-div.SPECI.doc 13/02/08 00 179 Dop I -Lys(Dopl1)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Thr-N- 2 Dop 1 -Lys(Dopl1)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Na-NH 2 Dop 1 -Lys(Dop 1 )-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH2, Dop I -Lys(Dop 1 )-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal- NH 2 Dop I -Lys(Dopl1)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop I -Lys(Dopl1)-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-oI, Dop I -Lys(DoplI)-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, 00 DpI-y(ol-y-~rDy-yl[y-h-~pLsTrCs-h-l 1 -Lys(Dopl1)L-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-o, ~Dop 1 -Lys(Dop2I)-D~yrDey-cyclo[Cys-he-DTrp-Lys-hr-Cys]r-Hr, Dopl1-Lys(Dop2)-D cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH2, Dop I -Lys(Dop2)-Ly- -~rcyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Trp- NH 2 Dop 1 -Lys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]l-Trp-NH2, Dop2-Lys(Dop2)-DPhe-cyclolCys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-Aepa-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, Dop2-Lys(Dop2)-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, Dop2-Lys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-Aepa-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop2-DLys(Dop2)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-Aepa-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-DLys(Dop2)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop2-DLys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-DLys(Dop2)-Aepa-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop2-Lys(Dop2)-D2Nal-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/O8 7 00 180 Do2LsDp)cco[y-yrDr-y-a-y]TrN 2 Dop2-Lys(Dop2)-yD-Dy-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys]-.Thr- NHp 2 LsDp)LsDy-~rccoCsTrDr-y-a-y]Tr Dop2-LsDp)Dy-,rcco[y-TrDr-y-a-y]TrN 5Dop2-Lys(Dop2)-D~yhe~y-cyclo[Cys-Tyr-DTrp-Lys- -Cys]-I-NH 2 Dop2-Lys(Dop2)-Dh-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop2-Lys(Dop2)-yDrDr-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2NaI- NH 2 00 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop2-Lys(Dop2)-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop2-Lys(Dop2)-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop2-Lys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop2-Lys(Dop2)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Trp-NH 2 Dop2-Lys(Dop2)- cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH 2 Dop2-Lys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys]-Trp- NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys]-Trp-NH 2 Dop3 -Lys(Dop3)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop3 -Lys(Dop3 )-Aepa-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop3 -Lys(Dop3 )-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop3 -Lys(Dop3 )-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop3 -Lys(Dop3 )-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop3 -DLys(Dop3)-DPhe-cyclollCys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, Dop3 -DLys(Dop3 )-Aepa-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop3 -DLys(Dop3 )-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop3 -DLys(Dop3)-Lys-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop3 -DLys(Dop3 )-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop3 -Lys(Dop3 )-D2NaI-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop3 -Lys(Dop3)-cyclo [Cys-Tyr-DTrp-Lys-VaI -Cys] -Thr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 181 00 Dop3 -Lys(Dop3)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Va1-Cys] -Thr- N NH 2 Dop3 -Lys(Dop3)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop3 -Lys(Dop3)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys]-2Na-NH 2 Dop3 -Lys(Dop3)-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop3 -Lys(Dop3 )-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal- NH 2 Dop3 -Lys(Dop3)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 00 Dop3 -Lys(Dop3)-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop3 -Lys(Dop3)-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop3 -Lys(Dop3)-Lys-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]l-Thr-ol, Dop3-Lys(Dop3)-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop3-Lys(Dop3)-DPhe-cyclollCys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH2, Dop3-Lys(Dop3 cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 Dop3-Lys(Dop3 )-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Va1-Cys] -Trp- NH 2 Dop3-Lys(Dop3)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Trp-NH 2 Dop4-Lys(Dop4)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-Lys(Dop4)-Aepa-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Tim-NH 2 Dop4-Lys(Dop4)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop4-Lys(Dop4)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop4-Lys(Dop4)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-DLys(Dop4)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-DLys(Dop4)-Aepa-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-DLys(Dop4)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop4-DLys(Dop4)-Lys-DTyr-DTyr-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 Dop4-DLys(Dop4)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop4-Lys(Dop4)-D2NaI-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop4-Lys(Dop4)-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI .doc 13/02/08 00 182 Dop4-Lys(Dop4)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Va1-Cys] -Thr- NH 2 Dop4-Lys(Dop4)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop4-Lys(Dop4)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH2, Dop4-Lys(Dop4)-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop4-Lys(Dop4)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal- No NH 2 Dop4-Lys(Dop4)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2NaI-NH 2 00 Dop4-Lys(Dop4)-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-oI, Dop4-Lys(Dop4)-cyclollCys-Phe-DTrp-Lys-Thr-Cys]-Thr-oI, Dop4-Lys(Dop4)-Lys-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-oI, Dop4-Lys(Dop4)-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop4-Lys(Dop4)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH 2 Dop4-Lys(Dop4)- cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH 2 Dop4-Lys(Dop4)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Trp- NH 2 Dop4-Lys(Dop4)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH 2 [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop5-Lys(Dop5)-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 NH 2 -Lys(Dop5)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 [Cys-Tyr-DTrp-Lys-Abu-Cys] -Tin-NH 2 Dop5-DLys(Dop5 )-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 NH 2 -Thr-NH 2 Dop5-Lys(Dop5)-D2Na1-cyclollCys-Tyr-DTrp-Lys-VaI-Cys] -Tin-NH 2 Dop5-Lys(Dop5)-cyclo[Cys-Tyr-DTrp-Lys-VaI-Cys] -Tin-NH 2 [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr- NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 00 183 TrN 2 2 [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 -2Nal- NH 2 ,cco[y-y-~r-y-h-Cs-Nl [CsTr-HpLy-h-Cs 2NlN [Cys-e-DTrp-Lys-Thr-Cys]--l N2 [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, 005LsDp)ccoCsPe-~pLsTrCs-h-l 00 Dop5-Lys(Dop5)-Lys-DTyr-DTyr-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-oI, -Trp-NH 2 cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH2, [Cys-Tyr-DTrp-Lys-VaI-Cys] -Trp- NH 2 Dop5-Lys(Dop5)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Trp-NH 2 Dop6-Lys(Dop6)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop6-Lys(Dop6)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop6-Lys(Dop6)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop6-Lys(Dop6)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop6-DLys(Dop6)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, Dop6-DLys(Dop6)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop6-DLys(Dop6)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop6-DLys(Dop6)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop6-Lys(Dop6)-D2Nal-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop6-Lys(Dop6)-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop6-Lys(Dop6)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr- NH 2 Dop6-Lys(Dop6)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop6-Lys(Dop6)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop6-Lys(Dop6)-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 00 184 Dop6-Lys(Dop6)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal- NH 2 Dop6-Lys(Dop6)-DTyr-DTyr-cyclolCys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH2, Dop6-Lys(Dop6)-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop6-Lys(Dop6)-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-oI, Dop6-Lys(Dop6)-Lys-DTyr-DTyr-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop6-Lys(Dop6)-DTyr-DTyr-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop6-Lys(Dop6)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 00 Dop6-Lys(Dop6)- cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH2, Dop6-Lys(Dop6)-Lys-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Trp- NH 2 Dop6-Lys(Dop6)-DTyr-DTyr-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Tmp-NH 2 Dop7-Lys(Dop7)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop7-Lys(Dop7)-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop7-DLys(Dop7)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, Dop7-DLys(Dop7)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop7-Lys(Dop7)-D2Na1-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop7-Lys(Dop7)-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop7-Lys(Dop7)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Nal-NH 2 Dop7-Lys(Dop7)-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2NaI-NH 2 Dop7-Lys(Dop7)-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop7-Lys(Dop7)-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop7-Lys(Dop7)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 Dop7-Lys(Dop7)- cyclollCys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH 2 Dop8-Lys(Dop8)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2, Dop8-Lys(Dop8)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop8-DLys(Dop8)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop8-DLys(Dop8)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop8-Lys(Dop8)-D2NaI-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop8-Lys(Dop8)-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop8-Lys(Dop8)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop8-Lys(Dop8)-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2NaI-NH 2 H!:\MaraR\Keep\Speci\P64463 -div-SPEC! .doc 13/02/08 185 00 Dop8-Lys(Dop8)-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop8-Lys(Dop8)-cyclo [Cys-Phe-DTrp-Lys-Thr.Cys]-Thr-oI, Dop8-Lys(Dop8)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Trp-NH 2 Dop8-Lys(Dop8)- cyclo[Cys-Tyr-DTrp-Lys-VaI-Cys]-Trp-NH 2 Dop9-Lys(Dop9)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop9-Lys(Dop9)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop9-DLys(Dop9)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop9-DLys(Dop9)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 00 Dop9-Lys(Dop9)-D2Na1-cyclo [Cys-Tyr-DTrp-Lys-VaI-Cys] -Thr-NH 2 Dop9-Lys(Dop9)-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop9-Lys(Dop9)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2NaI-NH 2 Dop9-Lys(Dop9)-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop9-Lys(Dop9)-DPhe-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dop9-Lys(Dop9)-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop9-Lys(Dop9)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 Dop9-Lys(Dop9)- cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH2, DopI1O-Lys(DoplIO)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop IO-Lys(Dop I )-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 DopI1O-DLys(Dopl1O)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop IO-DLys(Dopl1 )-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop I -Lys(DoplIO)-D2Na1-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 DopI1O-Lys(DoplI )-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 DopI1 -Lys(Dopl1 )-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 DopI1O-Lys(Dopl1 )-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2NaI -NH 2 Dop IO-Lys(DoplIO)-DPhe-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dop IO-Lys(Dopl1 )-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-oI, Dop I -Lys(Dopl1 )-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Va1-Cys]-Trp-NH 2 Dop I -Lys(Dop 10)- cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH 2 Dopl I -Lys(Dop II )-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dopl I -Lys(Dopl II)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dopl 11-DLys(Dopl 11)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 186 00 Dopl 11-DLys(Dopl 11)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dopl 11-Lys(Dopl 11)-D2NaI-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dopl 11-Lys(Dopl 11)-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dopl 11-Lys(Dopl 11)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dopl 11-Lys(Dopl 11)-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Na-NH 2 Dop 11I -Lys(Dopl 11)-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, Dopl 11-Lys(Dopl 11)-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-oI, 00 Dop I11 -Lys(Dop 11 )-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH 2 Dop II-Lys(Dopl 1 cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH 2 DoplI2-Lys(DoplI2)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dopl12-Lys(Dopl12)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dopl12-DLys(Dopl12)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 DoplI2-DLys(Dopl12)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 DopI 2-Lys(DopI 2)-D2Na1-cyclojlCys-Tyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dopl12-Lys(DoplI2)-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 DoplI2-Lys(DoplI2)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys] -2NaI-NH 2 DoplI2-Lys(DoplI2)-cyclo [Cys-Tyr-DTrp-Lys-Thr-Cys]-2Na-NH 2 Dopl12-Lys(DoplI2)-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-oI, DoplI2-Lys(Dopl12)-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Dopl12-Lys(Dopl12)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH2, Dopl12-Lys(Dop 12)- cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 Dop 1 3-Lys(Dop 1 3)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 DoplI3-Lys(DoplI3)-cyclo [Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dopl 13-DLys(Dopl I )-DPhe-cycloI[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop13 -DLys(Dop13 )-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop 1 3-Lys(Dop I 3)-D2Na1-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop 1 3-Lys(Dop I 3)-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop 1 3-Lys(Dop 1 3)-DPhe-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop 1 3-Lys(Dop I 3)-cyclo[Cys-Tyr-DTrp-Lys-Thr-Cys] -2Nal-NH 2 Dop I 3-Lys(Dop 1 3)-DPhe-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol, Hl:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 00 187 Dopl 13-Lys(Dop 1 3)-cyclo [Cys-Phe-DTrp-Lys-Thr-Cys] -Thr-ol, DopI 13-Lys(Dop 1 3)-DPhe-cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 Dop13 -Lys(Dop 13)- cyclo [Cys-Tyr-DTrp-Lys-Val-Cys] -Trp-NH 2 Dop 1 -Lys(Dop 1 )-Caeg-cyc lo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dopi -Lys(Dopl )-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-NH 2 Dop 1 -DLys(Dop I )-Caeg-cyclo [DCys-3 Pal- DTrp- Lys-DCys] -Thr(BzI)-Tyr- NH 2 Dop 1 -DLys(DoplI)-Caeg-cyclo [DCys-Phe.DTrp-Lys-DCys] -Ser(BzI)-Tyr-NH 2 00 Dop 1 -Lys(Dop I )-Lys-Caeg-cyclo [DCys-3 PaI-DTrp-Lys-DCys] -Thr(Bzi)-Tyr- NH 2 Dop I Lys(Dop 1 )-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DC ys] -Ser(BzI)-Tyr- NH 2 Dop 1 -DLys(Dop 1 )-Lys-Caeg-cyclo [DCys-3 PaI-DTrp-Lys-DCys] -Thr(Bzl)-Tyr- NH 2 Dop 1 -DLys(Dop 1 )-Lys- Caeg-cyclo [DCys-Phe-DTrp- Lys-DCys] -Ser(BzI)-Tyr- NH 2 Dop I -Lys(Dop 1 )-Aepa-Caeg-cyclo [DCys-3 Pal -DTrp- Lys-DCys] -Thr(BzI)-Tyr- NH4 2 Dop I -Lys(Dop I )-Aepa-Caeg-cyclo [DCys-Phe-DTrp- Lys-DCys] -Ser(BzI)-Tyr- NH 2 Dopi -DLys(Dopl )-Aepa-Caeg-cyclo[DCys-3Pal-DTrp-Lys-DCys]-Thr(BzI)- Tyr-NH 2 Dopl -DLys(Dopl )-Aepa-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)- Tyr-NH 2 Dop I -Lys(Dopl1)-Lys-Aepa-Caeg-cyclo [DCys-3 PaI-DTrp-Lys-DCys] -Thr(BzI)- Tyr-NH 2 Dopi -Lys(Dopl)-Lys-Aepa-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)- Tyr-NH 2 Dop I -DLys(DoplI)-Lys-Aepa-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys]- Thr(Bzl)-Tyr-NH 2 Dop I -DLys(Dop I )-Lys-Aepa-Caeg-cyc lo [DCys- Phe-DTrp- Lys- DCys] Ser(Bzl)-Tyr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECIdoc 13/02/08 00 188 Do2LsDp)Ce-yl Dy-PlDr-y-0s-h(z)TrN 2 Dop2-Lys(Dop2)-Caeg-cyclo[DCys-Pe-DTrp-Lys-DCys]-er(Bzl)-Tyr-NH 2 Dop2-Lys(Dop2)-Caeg-cycoIDCys-Pa-DTrp-Lys-DCys]-Tr(Bz)-Tyr-2 NH 2 Dop2-DLys(Dop2)-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 Dop2-Lys(Dop2)-Lys-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys]-Thr(Bzl)-Tyr- No NH 2 Dop2-Lys(Dop2)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(BzI)-Tyr- 00 NH 2 Dop2-DLys(Dop2)-Lys-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(BzI)-Tyr- NH 2 Dop2-DLys(Dop2)-Lys-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr- NH 2 Dop2-Lys(Dop2)-Aepa-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr- NH 2 Dop2-Lys(Dop2)-Aepa-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bz)-Tyr- NH 2 Dop2-DLys(Dop2)-Aepa-Caeg-cyc lo [DCys-3 PalI-DTrp-Lys-DCys] -Thr(Bzl)- Tyr-NH 2 Dop2-DLys(Dop2)-Aepa-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)- Tyr-NH 2 Dop2-Lys(Dop2)-Lys-Aepa-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys]-Thr(BzI)- Tyr-NH 2 Dop2-Lys(Dop2)-Lys-Aepa-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)- Tyr-NH 2 Dop2-DLys(Dop2)-Lys-Aepa-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys]- Thr(BzI)-Tyr-NH 2 Dop2-DLys(Dop2)-Lys-Aepa-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]- Ser(Bzl)-Tyr-NH 2 Dop3 -Lys(Dop3)-Caeg-cyclo [DCys-3 PalI-DTrp-Lys-DC ys] -Thr(Bzl)-Tyr-N H 2 Dop3 -Lys(Dop3 )-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bz)-Tyr-NH 2 H:\Maraf\Keep\Speci\P64463-div-SPECIdoc 13/02/08 189 00 Dop3 -Lys(Dop3)-Lys-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thir(Bzl)-Tyr- NH 2 Dop3 -Lys(Dop3 )-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr- NH 2 Dop3 -Lys(Dop3)-Aepa-Caeg-cyclo [DC ys-3 Pal- DTrp- Lys-DCys] -Thr(Bzl)-Tyr- NH1 2 Dop3 -Lys(Dop3)-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(BzI)-Tyr- NH 2 00 Dop3 -DLys(Dop3)-Caeg-cyclo [DCys-3 Pal- DTrp- Lys-DCys] -Thr(BzI)-Tyr- NH 2 Dop3 -DLys(Dop3 )-Caeg-cyclo [DCys-Phe-DTrp- Lys- DCys] -Ser(Bzl)-Tyr-N H 2 Dop3 -DLys(Dop3)-Lys-Caeg-cyclo [DCys-3 PaI-DTrp-Lys-DCys] -Thr(Bzl)-Tyr- NH 2 Dop3 -DLys(Dop3)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(BzI)-Tyr- NH 2 Dop3 -DLys(Dop3 )-Aepa-Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(Bzl)- Tyr-NH 2 Dop3 -DLys(Dop3)-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)- Tyr-NH 2 Dop4-Lys(Dop4)-Caeg-cyclo [DCys-3Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop4-Lys(Dop4)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr-NH 2 Dop4-Lys(Dop4)-Lys-Caeg-cyclo [DCys-3 PalI-DTrp-Lys-DCys] -Thr(BzI)-Tyr- NH1 2 Dop4-Lys(Dop4)-Lys-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr- NH1 2 Dop4-Lys(Dop4)-Aepa-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr- NH1 2 Dop4-Lys(Dop4)-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr- NH 2 Dop4-Lys(Dop4)-Lys-Aepa-Caeg-cyclo [DCys-3 Pal-DTrp- Lys- DCys] -Thr(Bzl)- Tyr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/0B 190 00 0 Dop4-Lys(Dop4)-Lys-Aepa-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)- N Tyr-NH- 2 Dop4-DLys(Dop4)-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(BzI)-Tyr- NH 2 Dop4-DLys(Dop4)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr-NH 2 Dop4-DLys(Dop4)-Lys-Caeg-cyclo[DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr- NH 2 Dop4-DLys(Dop4)-Lys-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr- 00 NH- 2 Dop4-DLys(Dop4)-Aepa-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys]-Thr(BzI)- Tyr-NH 2 Dop4-DLys(Dop4)-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)- Tyr-NH 2 Dop4-D Lys(Dop4)-Lys-Aepa-Caeg-cyclo [DCys-3 PalI-DTrp- Lys-DCys] Thr(Bzl)-Tyr-NH 2 Dop4-DLys(Dop4)-Lys-Aepa-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]- Ser(Bzl)-Tyr-NH 2 Dop5-Lys(Dop5)-Caeg-cyclo[DCys-3 PaI-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 -Ser(Bzl)-Tyr-NH 2 Dop5-DLys(Dop5)-Caeg-cyclo[DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr- NH- 2 [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr-NH 2 [DCys-3 Pal-DTrp-Lys-DCys] -Thr(BzI)-Tyr- NH- 2 Dop5-Lys(Dop5)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr- NH 2 )-Lys-Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(BzI)-Tyr- NH 2 )-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr- NH 2 Dop6-Lys(Dop6)-Caeg-cyclo [DCys-3 PaI-DTrp-Lys-DCys] -Thr(Bzl)-Tyr-NH 2 Dop6-Lys(Dop6)-.Caeg-cyclo[D~ys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr-NH 2 H:\MaraR\Keep\Speci\P64463 -div-SPEC! .doc 13/02/08 191 00 0 ~Dop6-DLys(Dop6)-Caeg-cyclo [DCys-3 Pal- DTrp- Lys-DCys] -Thr(Bzl)-Tyr- N NH 2 Dop6-DLys(Dop6)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr-NH 2 Dop6-Lys(Dop6)-Lys-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys] -Thr(Bzl)-Tyr- NH 2 Dop6-Lys(Dop6)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr- NH 2 Dop6-DLys(Dop6)-Lys-Caeg-cyclo[DCys-3 Pal-DTrp-Lys-DCys]-Thr(BzI)-Tyr- 00 NH 2 Dop6-DLys(Dop6)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr- NH 2 Dop7-Lys(Dop7)-Caeg-cyclo [DCys-3 Pal-DTrp-Lys-DCys]-Thr(Bzl)-Tyr-NH 2 Dop7-Lys(Dop7)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr-NH 2 Dop7-Lys(Dop7)-Lys-Caeg-cyclo[DCys-3 Pal-DTrp-Lys-DCys]-Thr(Bzl)-Tyr- NH 2 Dop7-Lys(Dop7)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(BzI)-Tyr- NH 2 Dop8-Lys(Dop8)-Caeg-cyclo [DCys-3Pal-DTrp-Lys-DCys]-Thr(Bz)-Tyr-NH 2 Dop8-Lys(Dop8)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(BzI)-Tyr-NH 2 Dop8-Lys(Dop8)-Lys-Caeg-cyclo[DCys-3 Pal-DTrp-Lys-DCys]-Thr(BzI)-Tyr- NH 2 Dop8-Lys(Dop8)-Lys-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr- NH 2 Dop9-Lys(Dop9)-Caeg-cyclo [DCys-3 PaI-DTrp-Lys-DCys]-Thr(Bzl)-Tyr-NH 2 Dop9-Lys(Dop9)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(BzI)-Tyr-NH 2 Dop9-Lys(Dop9)-Lys-Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DCys] -Thr(BzI)-Tyr- NH 2 Dop9-Lys(Dop9)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr- NH- 2 Dop 1 O-Lys(Dop 1 O)-Caeg-cyclo [DCys-3 Pal -DTrp- Lys-DCys] -Thr(Bzl)-Tyr- NH 2 H:\MaraR\Keep\Speci\P64463-diV-SPECI.doc 13/02/08 192 00 Dop 1 O-Lys(Dopl I )-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(Bzl)-Tyr- NH 2 Dop 1 O-Lys(Dop 1 O)-Lys-Caeg-cyclo[DCys-3Pal-DTrp-Lys-DCys]-Thr(BzI)- Tyr-NH 2 Dop 1 O-Lys(Dop I O)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bz1)-Tyr- NH- 2 Dop I1I -Lys(Dop 11 )-Caeg-cyclo [DCys-3 Pal -DTrp-Lys-DC ys] -Thr(Bz1)-Tyr- NH 2 00 DopI 11-Lys(Dopl 11)-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr- NH- 2 Dop 11 -Lys(Dop 11 )-Lys-Caeg-cyc lo [DCys-3 Pal- DTrp- Lys-DCys] -Thr(BzI)- Tyr-NH- 2 DopI 11-Lys(Dopl 11)-Lys-Caeg-cyclo [DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr- NH- 2 Dopi 2-Lys(Dopl2)-Caeg-cyclo[DCys-3Pal-DTrp-Lys-DCys]-Thr(BzI)-Tyr- NH- 2 Dopi 2-Lys(Dopl 2)-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr- NH- 2 Dop I 2-Lys(Dop 1 2)-Lys-Caeg-cyclo [DCys-3 PalI-DTrp- Lys-DCys] -Thr(Bz)- Tyr-NH 2 DoplI2-Lys(Dopl12)-Lys-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys] -Ser(BzI)-Tyr- NH7 2 Dopi 13-Lys(DoplI 3)-Caeg-cyclo [DCys-3 Pal- DTrp-Lys-DCys] -Thr(Bzl)-Tyr- NH 2 Dopl13-Lys(Dopl13)-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bzl)-Tyr- NH- 2 Dop 13 -Lys(Dop 1 3)-Lys-Caeg-cycl o[DCys-3 Pal- DTrp-Lys-DCys] -Thr(Bzl)- Tyr-NH 2 Dopi 3-Lys(Dopl 3)-Lys-Caeg-cyclo[DCys-Phe-DTrp-Lys-DCys]-Ser(Bz)-Tyr- NH 2 Dopi -Lys(DopI )-cyclo[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH 2 DoplI-Lys(DoplI)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 H:\MaraR\Keep\SpeCi\P64463-div-SPEcr.doc 13/02/08 00 193 0 Dop I -DLys(DoplI)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop I -DLys(Dopl1)-DPhe-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop 1 -Lys(DoplI)-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop 1 -DLys(Dop 1 )-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH 2 Dop2-Lys(Dop2)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH 2 Dop2-DLys(Dop2)-DPhe-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH2, 00 Dop2-Lys(Dop2)-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop3 -Lys(Dop3)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop3 -Lys(Dop3)-DPhe-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop3 -Lys(Dop3)-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop4-Lys(Dop4)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH 2 Dop4-Lys(Dop4)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH2, Dop4-Lys(Dop4)-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 -Lys(Dop5)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-NH 2 Dop5-DLys(Dop5 )-DPhe-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop6-Lys(Dop6)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop6-Lys(Dop6)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop6-DLys(Dop6)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop6-DLys(Dop6)-DPhe-cyclo[Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH2, Dop6-Lys(Dop6)-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop6-DLys(Dop6)-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop7-Lys(Dop7)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop7-Lys(Dop7)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop7-Lys(Dop7)-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop8-Lys(Dop8)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 00 194 Dop8-Lys(Dop8)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -ThT-NH 2 Dop9-Lys(Dop9)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop9-Lys(Dop9)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop I O-Lys(Dop I 0)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop I O-Lys(Dopl I )-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop 11I -Lys(Dop 11 )-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dopl I-Lys(Dopl 11)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dopl12-Lys(DoplI2)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 00 Dopl12-Lys(Dop I2)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop13 -Lys(Dopl13)-cyclo [Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys] -NH 2 Dop13 -Lys(DoplI3)-DPhe-cyclo [Cys-Phe-(N-Me)DTrp-Lys-Thr-Cys] -Thr-NH 2 DoplI-DPhe-cyclo[Cys-31ITyr(Dopl1)-DTrp-Lys-Val-Cys]-Thr-NH 2 DoplI-DPhe-Doc-DPhe-cyclo [Cys-31ITyr(Dopl1)-DTrp-Lys-Val-Cys]-Thr-NH 2 Dopl1-DLys(Dopl1)-DPhe-cyclo[Cys-31ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dopl1-DLys(Dopl1)-Aepa-DPhe-cyclolCys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dopl1-Lys(DoplI)-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 DoplI-Lys(Dopl1)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 DoplI-Lys(Dopl1)-Aepa-DPhe-cyclo[Cys-31ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop I -DLys(Dop I )-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop 1 Lys(Dop 1 )-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop I -Lys(Dop I )-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr- NH 2 Dop I -DLys(DoplI)-DTyr-DTyr-cyclo[Cys-31ITyr-DTrp-Lys-Thr-Cys]l-Thr-NH2, Dop I -DLys(Dopl1)-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr- NH 2 Dop 1 -DLys(Dop 1l)-DPhe-cyclo [Cys-31ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop I -DLys(Dopl1)-Aepa-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 Dop I -Lys(DoplI)-DTyr-DTyr-cyclo[Cys-31ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI .doc 13/02/08 195 00 Dop 1 -Lys(DoplI)-DPhe-cyclo [Cys-31ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop 1 -Lys(Dop l )-Aepa-DPhe-cyclo [Cys-31ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop I -DLys(DoplI)-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop I -Lys(DoplI)-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop I -Lys(Dopl1)-Lys-DTyr-DTyr-cyclo [Cys-31ITyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop I -DLys(Dopl1)-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 00 Dop I -DLys(Dop I )-Lys-DTyr-DTyr-cyclo [Cys-3 LTyr-DTrp-Lys-Abu-Cys]-Thr- NH 2 Dop I -DLys(Dopl )-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Va-Cys]-Thr-NH 2 Dop I -DLys(Dop I )-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr-NH2, Dop 1 -Lys(Dop 1 )-DTyr-DTyr-cyclo[Cys-3 LTyr-DTrp-Lys-VaI-Cys]-Thr-NH 2 Dop 1 -Lys(Dop I )-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Va1-CysI-Thr-NH 2 Dop I -Lys(Dop 1 )-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop I -DLys(Dop 1 )-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop I -Lys(Dop I )-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop I -Lys(Dop I)-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys] -Tin- NH 2 Dop 1 -DLys(DoplI)-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop 1 -DLys(DoplI)-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys] -Tin- NH 2 Dop2-DPhe-cyclo [Cys-3 ITyr(Dop2)-DTrp-Lys-VaI-Cys] -Tin-NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Tin-Cys] -Tin-NH 2 Dop2-Lys(Dop2)-Aepa-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Thn-Cys] -Tin- NH 2 Dop2-Lys(Dop2)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Tin-NH 2 Dop2-Lys(Dop2)-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Tin-NH 2 Dop2-DLys(Dop2)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 00 196 0o2Dy(o2-eaDh-yl Cs3Iy-~pLsTrCslTrN 2 Dop2-DLys(Dop2)-eDh-cyclo [Cys-3 Tyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-cycloCys-3 Tyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop2-Lys(Dop2)LyDrDr-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr- NH 2 LsDp)LsDy-~rccoCs3~rDr-y-h-y]Tr 5Dop2-Dy(o2-,rDy-yl Cs3Iy-~pLsTrCs TrN 2 Dop2-DLys(Dop2)-Aepa-DTyr-Dcyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-rN2 Thr-H 2 p)Ap-Dy-~rcco[y-ly-~p-y-h-y] 00-N2 00 Dop2-DLys(Dop2)-Lys-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr- NH 2 Dop2-DLys(Dop2)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-DLys(Dop2)-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-Aepa-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop2-DLys(Dop2)-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop2-DLys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 Dop2-DLys(Dop2)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop2-DLys(Dop2)-Aepa-DPhe-cyclo [Cys-3ITyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Val-Cys] -Thr-NH 2 Dop2-Lys(Dop2)-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop2-DLys(Dop2)-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr-NH 2 H:\MaraR\Keep\Speci\P64463-div-SPECI.doc 13/02/08 197 00 Dop2-Lys(Dop2)-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr-NH 2 Dop2-Lys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-VaI-Cys]-Thr- NH 2 Dop2-DLys(Dop2)-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys] -Thr-NH 2 s Dop2-DLys(Dop2)-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys] -Tin- NH 2 Dop3 -Lys(Dop3)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop4-Lys(Dop4)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 00 Dop3 -Lys(Dop3)-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop4-Lys(Dop4)-Aepa-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 [Cys-3 lTyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 [Cys-3 ITyr'-DTrp-Lys-Thr-Cys]-Thr-NH 2 -Lys(Dop5)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop5-DLys(Dop5)-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop5-Lys(Dop5)-Lys-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Tin- NH 2 -DLys(Dop5)-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop5-DLys(Dop5)-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr- NH 2 )-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 [Cys-3 ITyr-DTrp-Lys-Abu-Cys)-Thr-NH 2 Dop5-Lys(Dop5)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-Cys]-Thr-NH 2 -DLys(Dop5)-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr-NH 2 Dop5-Lys(Dop5)-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-CysI-Thr-NH 2 [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thn- NH 2 Dop5 -DLys(Dop5 )-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 HA\Ma-aR\Keep\Speci\P64463-div-SPECIdoc 13/02/08 198 Dop5-DLys(Dop5)-Lys-DTyr-DTyr-cyclo[Cys-3 ITyr-DTrp-Lys-Abu-Cys] -Thr- NH 2 -DLys(Dop5)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr-NH 2 -Lys(Dop5)-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr-NH 2 [Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr-NH 2 [Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr-NH2, Dop5-Lys(Dop5)-cyclolCys-3 ITyr-DTrp-Lys-Val-Cys] -Thr-NH 2 00 Dop5-Lys(Dop5)-Lys-DTyr-DTyr-cyclo [Cys-3 ITyr-DTrp-Lys-Val-Cys]-Thr- NH 2 [Cys-3 ITyr-DTrp-Lys-VaI-Cys]-Thr-NH 2 -DLys(Dop5)-Lys-DTyr-DTyr-cyclofCys-3 ITyr-DTrp-Lys-Val-Cys] -Thr- NH- 2 Dop6-Lys(Dop6)-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop7-Lys(Dop7)-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop8-Lys(Dop8)-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop9-Lys(Dop9)-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop 1 O-Lys(Dop 1 0)-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop I1I -Lys(Dop 11 )-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop I 2-Lys(Dop 1 2)-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-N H 2 Dop 13 -Lys(Dop 1 3)-cycl o[Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-NH 2 Dop6-Lys(Dop6)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop7-Lys(Dop7)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop8-Lys(Dop8)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop9-Lys(Dop9)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dop I O-Lys(Dop 1 O)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys] -Thr-N H 2 Dopl 11-Lys(Dopl 11)-DPhe-cyclo [Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 Dopl12-Lys(DoplI2)-DPhe-cyclo[Cys-3 ITyr-DTrp-Lys-Thr-Cys]-Thr-NH 2 or Dopl13-Lys(Dopl13)-DPhe-cyclo[Cys-3 lTyr-DTrp-Lys-Thr-Cys]- Thr-NH 2 or a pharmaceutically acceptable salt thereof, wherein said therapeutically effective amount is the amount effective to treat gastrointestinal bleeding in said patient. H:\?araR\Keep\Speci\P64463-div-SPECIdoc 13/02/08