NO830178L - Fremgangsmaate ved fremstilling av insulinderivater - Google Patents

Fremgangsmaate ved fremstilling av insulinderivater

Info

Publication number: NO830178L
Authority: NO; Norway
Prior art keywords: insulin; reaction; amino acid; character; approx
Prior art date: 1981-05-20

Application number

NO830178A

Other languages

English (en)

Norwegian (no)

Inventor

Finn Hede Andresen

Per Balschmidt

Original Assignee

Nordisk Insulinlab

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1981-05-20

Filing date

1983-01-19

Publication date

1983-01-19

1983-01-19 Application filed by Nordisk Insulinlab filed Critical Nordisk Insulinlab

1983-01-19 Publication of NO830178L publication Critical patent/NO830178L/no

Links

NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical class N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 title claims description 73
238000000034 method Methods 0.000 title claims description 32
238000002360 preparation method Methods 0.000 title description 2
102000004877 Insulin Human genes 0.000 claims description 30
108090001061 Insulin Proteins 0.000 claims description 30
229940125396 insulin Drugs 0.000 claims description 27
238000006243 chemical reaction Methods 0.000 claims description 19
108010005991 Pork Regular Insulin Proteins 0.000 claims description 15
108090000631 Trypsin Proteins 0.000 claims description 13
102000004142 Trypsin Human genes 0.000 claims description 13
229940024606 amino acid Drugs 0.000 claims description 13
239000012588 trypsin Substances 0.000 claims description 13
150000001413 amino acids Chemical class 0.000 claims description 12
239000003960 organic solvent Substances 0.000 claims description 9
102000004190 Enzymes Human genes 0.000 claims description 8
108090000790 Enzymes Proteins 0.000 claims description 8
108091005804 Peptidases Proteins 0.000 claims description 8
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims description 7
102000035195 Peptidases Human genes 0.000 claims description 7
238000004519 manufacturing process Methods 0.000 claims description 7
239000004473 Threonine Substances 0.000 claims description 5
229960002898 threonine Drugs 0.000 claims description 5
238000003776 cleavage reaction Methods 0.000 claims description 4
125000006239 protecting group Chemical group 0.000 claims description 4
230000007017 scission Effects 0.000 claims description 4
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 3
230000008569 process Effects 0.000 claims description 3
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
125000003368 amide group Chemical group 0.000 claims description 2
230000002255 enzymatic effect Effects 0.000 claims description 2
241000590020 Achromobacter Species 0.000 claims 1
125000001433 C-terminal amino-acid group Chemical group 0.000 claims 1
239000004365 Protease Substances 0.000 claims 1
102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims 1
125000005907 alkyl ester group Chemical group 0.000 claims 1
150000001408 amides Chemical class 0.000 claims 1
150000001735 carboxylic acids Chemical class 0.000 claims 1
239000003795 chemical substances by application Substances 0.000 claims 1
125000004185 ester group Chemical group 0.000 claims 1
230000002797 proteolythic effect Effects 0.000 claims 1
239000000203 mixture Substances 0.000 description 19
101000976075 Homo sapiens Insulin Proteins 0.000 description 18
PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 description 15
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
239000011541 reaction mixture Substances 0.000 description 13
235000001014 amino acid Nutrition 0.000 description 11
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
238000006460 hydrolysis reaction Methods 0.000 description 8
238000004458 analytical method Methods 0.000 description 7
239000000243 solution Substances 0.000 description 7
-1 amino acid ester Chemical class 0.000 description 6
238000004128 high performance liquid chromatography Methods 0.000 description 6
230000007062 hydrolysis Effects 0.000 description 6
239000008351 acetate buffer Substances 0.000 description 5
229960000583 acetic acid Drugs 0.000 description 5
PIEPQKCYPFFYMG-UHFFFAOYSA-N tris acetate Chemical compound CC(O)=O.OCC(N)(CO)CO PIEPQKCYPFFYMG-UHFFFAOYSA-N 0.000 description 5
102000000496 Carboxypeptidases A Human genes 0.000 description 4
108010080937 Carboxypeptidases A Proteins 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 4
239000004026 insulin derivative Substances 0.000 description 4
241001465754 Metazoa Species 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
TVHCXXXXQNWQLP-DMTCNVIQSA-N methyl (2s,3r)-2-amino-3-hydroxybutanoate Chemical compound COC(=O)[C@@H](N)[C@@H](C)O TVHCXXXXQNWQLP-DMTCNVIQSA-N 0.000 description 3
230000035484 reaction time Effects 0.000 description 3
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 2
229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 2
241000283690 Bos taurus Species 0.000 description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
MQUQNUAYKLCRME-INIZCTEOSA-N N-tosyl-L-phenylalanyl chloromethyl ketone Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N[C@H](C(=O)CCl)CC1=CC=CC=C1 MQUQNUAYKLCRME-INIZCTEOSA-N 0.000 description 2
101000993800 Sus scrofa Insulin Proteins 0.000 description 2
AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
230000009471 action Effects 0.000 description 2
125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 2
235000012538 ammonium bicarbonate Nutrition 0.000 description 2
239000001099 ammonium carbonate Substances 0.000 description 2
239000000872 buffer Substances 0.000 description 2
239000007853 buffer solution Substances 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
238000004108 freeze drying Methods 0.000 description 2
150000002500 ions Chemical class 0.000 description 2
239000007788 liquid Substances 0.000 description 2
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 2
108090000765 processed proteins & peptides Proteins 0.000 description 2
238000000746 purification Methods 0.000 description 2
239000000376 reactant Substances 0.000 description 2
DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 2
238000007086 side reaction Methods 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
239000007858 starting material Substances 0.000 description 2
PZUOEYPTQJILHP-GBXIJSLDSA-N (2s,3r)-2-amino-3-hydroxybutanamide Chemical compound C[C@@H](O)[C@H](N)C(N)=O PZUOEYPTQJILHP-GBXIJSLDSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
229920000936 Agarose Polymers 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
XUUXCWCKKCZEAW-YFKPBYRVSA-N Arg-Gly Chemical compound OC(=O)CNC(=O)[C@@H](N)CCCN=C(N)N XUUXCWCKKCZEAW-YFKPBYRVSA-N 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
101001011741 Bos taurus Insulin Proteins 0.000 description 1
GUBGYTABKSRVRQ-WFVLMXAXSA-N DEAE-cellulose Chemical compound OC1C(O)C(O)C(CO)O[C@H]1O[C@@H]1C(CO)OC(O)C(O)C1O GUBGYTABKSRVRQ-WFVLMXAXSA-N 0.000 description 1
241000282412 Homo Species 0.000 description 1
101000856199 Homo sapiens Chymotrypsin-like protease CTRL-1 Proteins 0.000 description 1
QOOWRKBDDXQRHC-BQBZGAKWSA-N L-lysyl-L-alanine Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H](N)CCCCN QOOWRKBDDXQRHC-BQBZGAKWSA-N 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
108010053229 Lysyl endopeptidase Proteins 0.000 description 1
229920005654 Sephadex Polymers 0.000 description 1
239000012507 Sephadex™ Substances 0.000 description 1
241000282887 Suidae Species 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
239000002253 acid Substances 0.000 description 1
235000004279 alanine Nutrition 0.000 description 1
238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
235000011114 ammonium hydroxide Nutrition 0.000 description 1
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
229960001230 asparagine Drugs 0.000 description 1
235000009582 asparagine Nutrition 0.000 description 1
IXIBAKNTJSCKJM-BUBXBXGNSA-N bovine insulin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 IXIBAKNTJSCKJM-BUBXBXGNSA-N 0.000 description 1
239000004202 carbamide Substances 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
238000011109 contamination Methods 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
206010012601 diabetes mellitus Diseases 0.000 description 1
238000001035 drying Methods 0.000 description 1
230000000694 effects Effects 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
239000012535 impurity Substances 0.000 description 1
238000002955 isolation Methods 0.000 description 1
238000004811 liquid chromatography Methods 0.000 description 1
238000011068 loading method Methods 0.000 description 1
239000011159 matrix material Substances 0.000 description 1
238000010647 peptide synthesis reaction Methods 0.000 description 1
229920002401 polyacrylamide Polymers 0.000 description 1
238000009958 sewing Methods 0.000 description 1
239000002904 solvent Substances 0.000 description 1
238000003756 stirring Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
230000007306 turnover Effects 0.000 description 1
239000000052 vinegar Substances 0.000 description 1
235000021419 vinegar Nutrition 0.000 description 1
239000011701 zinc Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/62—Insulins
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/582—Recycling of unreacted starting or intermediate materials

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Biochemistry (AREA)
Genetics & Genomics (AREA)
Gastroenterology & Hepatology (AREA)
Toxicology (AREA)
Endocrinology (AREA)
Biophysics (AREA)
General Health & Medical Sciences (AREA)
Zoology (AREA)
Medicinal Chemistry (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Diabetes (AREA)
Peptides Or Proteins (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

NO830178A 1981-05-20 1983-01-19 Fremgangsmaate ved fremstilling av insulinderivater NO830178L (no)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
DK222181		1981-05-20

Publications (1)

Publication Number	Publication Date
NO830178L true NO830178L (no)	1983-01-19

Family

ID=8110884

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO830178A NO830178L (no)	1981-05-20	1983-01-19	Fremgangsmaate ved fremstilling av insulinderivater

Country Status (5)

Country	Link
EP (1)	EP0079362A1 (fr)
JP (1)	JPS58500739A (fr)
AU (1)	AU8457482A (fr)
NO (1)	NO830178L (fr)
WO (1)	WO1982004069A1 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0087238A1 (fr) *	1982-02-08	1983-08-31	Biogen N.V.	Méthode de préparation d'insuline humaine à partir d'insuline non-humaine-
EP0092829B1 (fr) *	1982-04-23	1990-11-07	Wako Pure Chemical Industries, Ltd.	Procédé pour la semi-synthèse d'insuline humaine et protéase alcaline pour sa mise en oeuvre

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AU545416B2 (en) *	1979-04-06	1985-07-11	Carlsberg Biotechnology Ltd. A/S	A process for enzymatic production of peptides
DK319780A (da) *	1980-07-24	1982-01-25	Forenede Bryggerier As	Fremgangsmaade til enzymatisk udskiftning af b-30 aminosyren i insuliner

1982
- 1982-05-19 WO PCT/DK1982/000045 patent/WO1982004069A1/fr not_active Ceased
- 1982-05-19 EP EP82901588A patent/EP0079362A1/fr not_active Withdrawn
- 1982-05-19 AU AU84574/82A patent/AU8457482A/en not_active Abandoned
- 1982-05-19 JP JP57501738A patent/JPS58500739A/ja active Pending
1983
- 1983-01-19 NO NO830178A patent/NO830178L/no unknown

Also Published As

Publication number	Publication date
EP0079362A1 (fr)	1983-05-25
WO1982004069A1 (fr)	1982-11-25
JPS58500739A (ja)	1983-05-12
AU8457482A (en)	1982-12-07

Publication	Publication Date	Title
EP0020290B1 (fr)	1984-07-11	Procédé pour scinder spécifiquement des séquences peptidiques des protéines
US4400465A (en)	1983-08-23	Semi-synthesis of human insulin
JP2007532096A (ja)	2007-11-15	アシル化されたインスリンの製造方法
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