WO2002052016A2 - Regulation of human protein l-isoaspartate o-methyltransferase-like enzyme - Google Patents
Regulation of human protein l-isoaspartate o-methyltransferase-like enzyme Download PDFInfo
- Publication number
- WO2002052016A2 WO2002052016A2 PCT/EP2001/015001 EP0115001W WO02052016A2 WO 2002052016 A2 WO2002052016 A2 WO 2002052016A2 EP 0115001 W EP0115001 W EP 0115001W WO 02052016 A2 WO02052016 A2 WO 02052016A2
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- WO
- WIPO (PCT)
- Prior art keywords
- polypeptide
- isoaspartate
- enzyme
- protein
- seq
- Prior art date
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- Ceased
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/573—Immunoassay; Biospecific binding assay; Materials therefor for enzymes or isoenzymes
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/10—Transferases (2.)
- C12N9/1003—Transferases (2.) transferring one-carbon groups (2.1)
- C12N9/1007—Methyltransferases (general) (2.1.1.)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
- C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/136—Screening for pharmacological compounds
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/158—Expression markers
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pathology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Urology & Nephrology (AREA)
- Medicinal Chemistry (AREA)
- Hematology (AREA)
- Physics & Mathematics (AREA)
- Cell Biology (AREA)
- Oncology (AREA)
- Hospice & Palliative Care (AREA)
- Food Science & Technology (AREA)
- Biophysics (AREA)
- General Physics & Mathematics (AREA)
- Enzymes And Modification Thereof (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Reagents that regulate human protein L-isoaspartate O-methyltransferase-like enzyme and reagents which bind to human protein L-isoaspartate O-methyltransferase-like enzyme gene products can play a role in preventing, ameliorating, or correcting dysfunctions or diseases including, but not limited to, cancer.
Claims
1. An isolated polynucleotide being selected from the group consisting of:
a) a polynucleotide encoding a protein L-isoaspartate O-methylfransferase- like enzyme polypeptide comprising an amino acid sequence selected form the group consisting of:
amino acid sequences which are at least about 88% identical to the amino acid sequence shown in SEQ ID NO: 2; and the amino acid sequence shown in SEQ ID NO: 2.
b) a polynucleotide comprising the sequence of SEQ ID NO: 1 ;
c) a polynucleotide which hybridizes under stringent conditions to a polynucleotide specified in (a) and (b) and encodes a protein L- isoaspartate O-methylfransferase-like enzyme polypeptide;
d) a polynucleotide the sequence of which deviates from the poly- nucleotide sequences specified in (a) to (c) due to the degeneration of the genetic code and encodes a protein L-isoaspartate O- methylfransferase-like enzyme polypeptide; and
e) a polynucleotide which represents a fragment, derivative or allelic variation of a polynucleotide sequence specified in (a) to (d) and encodes a protein L-isoaspartate O-methylfransferase-like enzyme polypeptide.
2. An expression vector containing any polynucleotide of claim 1.
3. A host cell containing the expression vector of claim 2.
76 -
4. A substantially purified protein L-isoaspartate O-methyltransferase-like enzyme polypeptide encoded by a polynucleotide of claim 1.
5. A method for producing a protem L-isoaspartate O-methylfransferase-like enzyme polypeptide, wherein the method comprises the following steps:
a) culturing the host cell of claim 3 under conditions suitable for the expression of the protein L-isoaspartate O-methylfransferase-like enzyme polypeptide; and
b) recovering the protein L-isoaspartate O-methyltransferase-like enzyme polypeptide from the host cell culture.
6. A method for detection of a polynucleotide encoding a protein L-isoaspartate
O-methylfransferase-like enzyme polypeptide in a biological sample comprising the following steps:
a) hybridizing any polynucleotide of claim 1 to a nucleic acid material of a biological sample, thereby forming a hybridization complex; and
b) detecting said hybridization complex.
7. The method of claim 6, wherein before hybridization, the nucleic acid material of the biological sample is amplified.
8. A method for the detection of a polynucleotide of claim 1 or a protein L- isoaspartate O-methylfransferase-like enzyme polypeptide of claim 4 comprising the steps of:
- 77 -
contacting a biological sample with a reagent which specifically interacts with the polynucleotide or the protein L-isoaspartate O-methylfransferase-like enzyme polypeptide.
9. A diagnostic kit for conducting the method of any one of claims 6 to 8.
10. A method of screening for agents which decrease the activity of a protein L- isoaspartate O-methyltransferase-like enzyme, comprising the steps of:
contacting a test compound with any protein L-isoaspartate O-methylfransferase-like enzyme polypeptide encoded by any polynucleotide of clai ! ;
detecting binding of the test compound to the protein L-isoaspartate O- methyltransferase-like enzyme polypeptide, wherein a test compound which binds to the polypeptide is identified as a potential therapeutic agent for decreasing the activity of a protein L-isoaspartate O-methyltransferase-like enzyme.
11. A method of screening for agents which regulate the activity of a protein L- isoaspartate O-methylfransferase-like enzyme, comprising the steps of:
contacting a test compound with a protein L-isoaspartate O-methyltransferase-like enzyme polypeptide encoded by any polynucleotide of claim 1; and
detecting a protein L-isoaspartate O-methyltransferase-like enzyme activity of the polypeptide, wherein a test compound which increases the protein L- isoaspartate O-methylfransferase-like enzyme activity is identified as a potential therapeutic agent for increasing the activity of the protein L- isoaspartate O-methyltransferase-like enzyme, and wherein a test compound which decreases the protein L-isoaspartate O-methylfransferase-like enzyme activity of the polypeptide is identified as a potential therapeutic agent for
78 -
decreasing the activity of the protein L-isoaspartate O-methyltransferase-like enzyme.
12. A method of screening for agents which decrease the activity of a protein L- isoaspartate O-methyltransferase-like enzyme, comprising the steps of:
contacting a test compound with any polynucleotide of claim 1 and detecting binding of the test compound to the polynucleotide, wherein a test compound which binds to the polynucleotide is identified as a potential therapeutic agent for decreasing the activity of protein L-isoaspartate O-methylfransferase-like enzyme.
13. A method of reducing the activity of protein L-isoaspartate O-methyltransferase- like enzyme, comprising the steps of:
contacting a cell with a reagent which specifically binds to any polynucleotide of claim 1 or any protein L-isoaspartate O-methyltransferase-like enzyme polypeptide of claim 4, whereby the activity of protein L-isoaspartate O- methyltransferase-like enzyme is reduced.
14. A reagent that modulates the activity of a protein L-isoaspartate O- methyltransferase-like enzyme polypeptide or a polynucleotide wherein said reagent is identified by the method of any of the claim 10 to 12.
15. A pharmaceutical composition, comprising: the expression vector of claim 2 or the reagent of claim 14 and a pharmaceutically acceptable carrier.
16. Use of the expression vector of claim 2 or the reagent of claim 14 in the preparation of a medicament for modulating the activity of a protein L- isoaspartate O-methyltransferase-like enzyme in a disease.
79 -
17. Use of claim 16 wherem the disease is cancer.
18. A cDNA encoding a polypeptide comprising the amino acid sequence shown in SEQ ID NO: 2.
19. The cDNA of claim 18 which comprises SEQ ID NO: 1.
20. The cDNA of claim 18 which consists of SEQ ID NO: 1.
21. An expression vector comprising a polynucleotide which encodes a polypeptide comprising the amino acid sequence shown in SEQ ID NO: 2.
22. The expression vector of claim 21 wherein the polynucleotide consists of SEQ JJD NO: l.
23. A host cell comprising an expression vector which encodes a polypeptide comprising the amino acid sequence shown in SEQ ID NO: 2.
24. The host cell of claim 23 wherein the polynucleotide consists of SEQ ID NO:
1.
25. A purified polypeptide comprising the amino acid sequence shown in SEQ ID NO: 2.
26. The purified polypeptide of claim 25 which consists of the amino acid sequence shown in SEQ ID NO: 2.
27. A fusion protein comprising a polypeptide having the amino acid sequence shown in SEQ ID NO: 2.
80
28. A method of producing a polypeptide comprising the amino acid sequence shown in SEQ ID NO: 2, comprising the steps of:
culturing a host cell comprising an expression vector which encodes the polypeptide under conditions whereby the polypeptide is expressed; and
isolating the polypeptide.
29. The method of claim 28 wherein the expression vector comprises SEQ ID NO: 1.
30. A method of detecting a coding sequence for a polypeptide comprising the amino acid sequence shown in SEQ ID NO: 2, comprising the steps of:
hybridizing a polynucleotide comprising 11 contiguous nucleotides of SEQ
ID NO: 1 to nucleic acid material of a biological sample, thereby forming a hybridization complex; and
detecting the hybridization complex.
31. The method of claim 30 further comprising the step of amplifying the nucleic acid material before the step of hybridizing.
32. A kit for detecting a coding sequence for a polypeptide comprising the amino acid sequence shown in SEQ ID NO: 2, comprising:
a polynucleotide comprising 11 contiguous nucleotides of SEQ ID NO: 1; and instructions for the method of claim 30.
33. A method of detecting a polypeptide comprising the amino acid sequence shown in SEQ ID NO: 2, comprising the steps of:
81
contacting a biological sample with a reagent that specifically binds to the polypeptide to form a reagent-polypeptide complex; and
detecting the reagent-polypeptide complex.
34. The method of claim 33 wherein the reagent is an antibody.
35. A kit for detecting a polypeptide comprising the amino acid sequence shown in SEQ ID NO: 2, comprising:
an antibody which specifically binds to the polypeptide; and
instructions for the method of claim 33.
36. A method of screening for agents which can modulate the activity of a human protein L-isoaspartate O-methylfransferase-like enzyme, comprising the steps of:
contacting a test compound with a polypeptide comprising an amino acid sequence selected from the group consisting of: (1) amino acid sequences which are at least about 88% identical to the amino acid sequence shown in SEQ ID NO: 2 and (2) the amino acid sequence shown in SEQ ID NO: 2; and
detecting binding of the test compound to the polypeptide, wherein a test compound which binds to the polypeptide is identified as a potential agent for regulating activity of the human protein L-isoaspartate O-methyltransferase- like enzyme.
37. The method of claim 36 wherein the step of contacting is in a cell.
- 82 -
38. The method of claim 36 wherein the cell is in vitro.
39. The method of claim 36 wherein the step of contacting is in a cell-free system.
40. The method of claim 36 wherein the polypeptide comprises a detectable label.
41. The method of claim 36 wherem the test compound comprises a detectable label.
42. The method of claim 36 wherein the test compound displaces a labeled ligand which is bound to the polypeptide.
43. The method of claim 36 wherein the polypeptide is bound to a solid support.
44. The method of claim 36 wherein the test compound is bound to a solid support.
45. A method of screening for agents which modulate an activity of a human protem L-isoaspartate O-methylfransferase-like enzyme, comprising the steps of:
contacting a test compound with a polypeptide comprising an amino acid sequence selected from the group consisting of: (1) amino acid sequences which are at least about 88% identical to the amino acid sequence shown in
SEQ TJD NO: 2 and (2) the amino acid sequence shown in SEQ ID NO: 2; and
detecting an activity of the polypeptide, wherein a test compound which increases the activity of the polypeptide is identified as a potential agent for increasing the activity of the human protein L-isoaspartate O-methyltransferase- like enzyme, and wherein a test compound which decreases the activity of the
- 83 -
polypeptide is identified as a potential agent for decreasing the activity of the human protein L-isoaspartate O-methylfransferase-like enzyme.
46. The method of claim 45 wherein the step of contacting is in a cell.
47. The method of claim 45 wherein the cell is in vitro.
48. The method of claim 45 wherein the step of contacting is in a cell-free system.
49. A method of screening for agents which modulate an activity of a human protein L-isoaspartate O-methylfransferase-like enzyme, comprising the steps of:
contacting a test compound with a product encoded by a polynucleotide which comprises the nucleotide sequence shown in SEQ ID NO: 1; and
detecting binding of the test compound to the product, wherein a test compound which binds to the product is identified as a potential agent for regulating the activity of the human protein L-isoaspartate O-methyltransferase-like enzyme.
50. The method of claim 49 wherein the product is a polypeptide.
51. The method of claim 49 wherein the product is RNA.
52. A method of reducing activity of a human protein L-isoaspartate O- methyltransferase-like enzyme, comprising the step of:
contacting a cell with a reagent which specifically binds to a product encoded by a polynucleotide comprising the nucleotide sequence shown in SEQ ID
- 84 -
NO: 1, whereby the activity of a human protein L-isoaspartate O- methyltransferase-like enzyme is reduced.
53. The method of claim 52 wherein the product is a polypeptide.
54. The method of claim 53 wherein the reagent is an antibody.
55. The method of claim 52 wherein the product is RNA.
56. The method of claim 55 wherein the reagent is an antisense oligonucleotide.
57. The method of claim 56 wherein the reagent is a ribozyme.
58. The method of claim 52 wherein the cell is in vitro.
59. The method of claim 52 wherein the cell is in vivo.
60. A pharmaceutical composition, comprising:
a reagent which specifically binds to a polypeptide comprising the amino acid sequence shown in SEQ ID NO: 2; and
a pharmaceutically acceptable carrier.
61. The pharmaceutical composition of claim 60 wherein the reagent is an antibody.
62. A pharmaceutical composition, comprising:
a reagent which specifically binds to a product of a polynucleotide comprising the nucleotide sequence shown in SEQ ID NO: 1; and
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a pharmaceutically acceptable carrier.
63. The pharmaceutical composition of claim 62 wherein the reagent is a ribozyme.
64. The pharmaceutical composition of claim 62 wherein the reagent is an antisense oligonucleotide.
65. The pharmaceutical composition of claim 62 wherein the reagent is an antibody.
66. A pharmaceutical composition, comprising:
an expression vector encoding a polypeptide comprising the amino acid sequence shown in SEQ ID NO: 2; and
a pharmaceutically acceptable carrier.
67. The pharmaceutical composition of claim 66 wherein the expression vector comprises SEQ ID NO: 1.
68. A method of treating a protein L-isoaspartate O-methylfransferase-like enzyme dysfunction related disease, wherein the disease is cancer comprising the step of:
administering to a patient in need thereof a therapeutically effective dose of a reagent that modulates a function of a human protein L-isoaspartate O- methylfransferase-like enzyme, whereby symptoms of the protein L- isoaspartate O-methylfransferase-like enzyme disfunction related disease are ameliorated.
- 86
69. The method of claim 68 wherein the reagent is identified by the method of claim 36.
70. The method of claim 68 wherein the reagent is identified by the method of claim 45.
71. The method of claim 68 wherein the reagent is identified by the method of claim 49.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2002217134A AU2002217134A1 (en) | 2000-12-26 | 2001-12-19 | Regulation of human protein l-isoaspartate o-methyltransferase-like enzyme |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US25729200P | 2000-12-26 | 2000-12-26 | |
| US60/257,292 | 2000-12-26 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO2002052016A2 true WO2002052016A2 (en) | 2002-07-04 |
| WO2002052016A3 WO2002052016A3 (en) | 2002-11-07 |
Family
ID=22975669
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP2001/015001 Ceased WO2002052016A2 (en) | 2000-12-26 | 2001-12-19 | Regulation of human protein l-isoaspartate o-methyltransferase-like enzyme |
Country Status (2)
| Country | Link |
|---|---|
| AU (1) | AU2002217134A1 (en) |
| WO (1) | WO2002052016A2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003057204A3 (en) * | 2002-01-08 | 2004-02-05 | Nordic Bioscience As | Modulation of iamt (pimt or pcmt) in immune system |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996012797A1 (en) * | 1994-10-19 | 1996-05-02 | The Regents Of The University Of California | Production and use of human and plant methyltransferases |
| WO1998015647A1 (en) * | 1996-10-08 | 1998-04-16 | Novartis Ag | Modulation of apoptosis |
| EP1074617A3 (en) * | 1999-07-29 | 2004-04-21 | Research Association for Biotechnology | Primers for synthesising full-length cDNA and their use |
| EP1328636A2 (en) * | 2000-09-01 | 2003-07-23 | Nuvelo Inc. | Nucleic acids and polypeptides |
-
2001
- 2001-12-19 AU AU2002217134A patent/AU2002217134A1/en not_active Abandoned
- 2001-12-19 WO PCT/EP2001/015001 patent/WO2002052016A2/en not_active Ceased
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003057204A3 (en) * | 2002-01-08 | 2004-02-05 | Nordic Bioscience As | Modulation of iamt (pimt or pcmt) in immune system |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2002052016A3 (en) | 2002-11-07 |
| AU2002217134A1 (en) | 2002-07-08 |
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