NZ801728B2 - ATF5 peptide variants and uses thereof - Google Patents
ATF5 peptide variants and uses thereof Download PDFInfo
- Publication number
- NZ801728B2 NZ801728B2 NZ801728A NZ80172819A NZ801728B2 NZ 801728 B2 NZ801728 B2 NZ 801728B2 NZ 801728 A NZ801728 A NZ 801728A NZ 80172819 A NZ80172819 A NZ 80172819A NZ 801728 B2 NZ801728 B2 NZ 801728B2
- Authority
- NZ
- New Zealand
- Prior art keywords
- seq
- atf5
- atf5 peptide
- peptide according
- examples
- Prior art date
Links
- 102100023582 Cyclic AMP-dependent transcription factor ATF-5 Human genes 0.000 title claims abstract 25
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract 22
- 101000905746 Homo sapiens Cyclic AMP-dependent transcription factor ATF-5 Proteins 0.000 title abstract 5
- 239000000203 mixture Substances 0.000 claims abstract 7
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims abstract 4
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims abstract 4
- 210000005170 neoplastic cell Anatomy 0.000 claims abstract 3
- 230000003013 cytotoxicity Effects 0.000 claims abstract 2
- 231100000135 cytotoxicity Toxicity 0.000 claims abstract 2
- 230000002401 inhibitory effect Effects 0.000 claims abstract 2
- 230000035755 proliferation Effects 0.000 claims abstract 2
- 230000001737 promoting effect Effects 0.000 claims abstract 2
- 101710182028 Cyclic AMP-dependent transcription factor ATF-5 Proteins 0.000 claims 20
- 230000000052 comparative effect Effects 0.000 claims 5
- 108020004707 nucleic acids Proteins 0.000 claims 4
- 102000039446 nucleic acids Human genes 0.000 claims 4
- 150000007523 nucleic acids Chemical class 0.000 claims 4
- 150000001413 amino acids Chemical group 0.000 claims 3
- 239000003814 drug Substances 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- RAVVEEJGALCVIN-AGVBWZICSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-5-amino-2-[[(2s)-2-[[(2s)-2-[[(2s)-6-amino-2-[[(2s)-6-amino-2-[[(2s)-2-[[2-[[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]hexanoyl]amino]-5-(diamino Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCN=C(N)N)NC(=O)CNC(=O)[C@@H](N)CC1=CC=C(O)C=C1 RAVVEEJGALCVIN-AGVBWZICSA-N 0.000 claims 1
- 108700000788 Human immunodeficiency virus 1 tat peptide (47-57) Proteins 0.000 claims 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 1
- 125000003368 amide group Chemical group 0.000 claims 1
- 210000004899 c-terminal region Anatomy 0.000 claims 1
- BHONFOAYRQZPKZ-LCLOTLQISA-N chembl269478 Chemical compound C([C@H](NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CCCNC(N)=N)[C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(O)=O)C1=CC=CC=C1 BHONFOAYRQZPKZ-LCLOTLQISA-N 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 102000004196 processed proteins & peptides Human genes 0.000 abstract 3
Classifications
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- 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
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- 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
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4702—Regulators; Modulating activity
- C07K14/4705—Regulators; Modulating activity stimulating, promoting or activating activity
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
- C07K2319/73—Fusion polypeptide containing domain for protein-protein interaction containing coiled-coiled motif (leucine zippers)
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
Abstract
Provided are ATF5 peptides having a truncated ATF5 leucine zipper region and, optionally, a cell-penetrating region, compositions comprising the ATF5 peptides, and methods of inhibiting proliferation of and promoting cytotoxicity in a neoplastic cell using the ATF5 peptides.
Claims (16)
1. An activating transcription factor 5 (ATF5) peptide comprising a truncated ATF5 leucine zipper region, wherein the truncated ATF5 leucine zipper region comprises an amino acid sequence selected from the group consisting of: i. LEGEGQGLEARNRELKERAESV (SEQ ID NO: 54); ii. LEGEAQGLEARNRELKERAESV (SEQ ID NO: 55); iii. LEGECQGLEARNRELKERAEAV (SEQ ID NO: 56); iv. LEGECQGLEARLRELKERAESV (SEQ ID NO: 57); v. LEGECAGLEARNRELKERAESV (SEQ ID NO: 58); vi. LEGRCQGLRAENRELEERAESV (SEQ ID NO: 59); vii. LEGRCQGLRAELRELEERAEAV (SEQ ID NO: 60); and viii. LEGRAQGLRAELRELEERAEAV (SEQ ID NO: 61); wherein the ATF5 peptide does not comprise an extended leucine zipper region.
2. The ATF5 peptide according to claim 1,further comprising a cell-penetrating region, wherein the ATF5 peptide is a cell-penetrating ATF5 peptide.
3. The ATF5 peptide according to claim 2, wherein the cell-penetrating region has an amino acid sequence selected from the group consisting of: RQIKIWFQNRRMKWKK (SEQ ID NO: 25), RQLKLWFQNRRMKWKK (SEQ ID NO: 26), YGRKKRRQRRR (SEQ ID NO: 40), and YGRKKRRQRR (SEQ ID NO: 41).
4. The ATF5 peptide according to claim 2, comprising an amino acid sequence selected from the group consisting of: i. RQIKIWFQNRRMKWKKLEGEGQGLEARNRELKERAESV (SEQ ID NO: 4); ii. RQIKIWFQNRRMKWKKLEGEAQGLEARNRELKERAESV (SEQ ID NO: 5); iii. RQIKIWFQNRRMKWKKLEGECAGLEARNRELKERAESV (SEQ ID NO: 8); iv. RQIKIWFQNRRMKWKKLEGRCQGLRAENRELEERAESV (SEQ ID NO: 9); v. RQIKIWFQNRRMKWKKLEGECQGLEARLRELKERAESV (SEQ ID NO: 7); vi. RQIKIWFQNRRMKWKKLEGECQGLEARNRELKERAEAV (SEQ ID NO: 6); vii. RQIKIWFQNRRMKWKKLEGRCQGLRAELRELEERAEAV (SEQ ID NO: 10); and viii. RQIKIWFQNRRMKWKKLEGRAQGLRAELRELEERAEAV (SEQ ID NO: 11).
5. The ATF5 peptide according to any one of the preceding claims, wherein the peptide comprises an N-terminal acetyl group and/or a C-terminal amide group.
6. A composition comprising the ATF5 peptide according to any one of the preceding claims.
7. The composition according to claim 6, which is a pharmaceutical composition.
8. A kit comprising the ATF5 peptide according to any one of claims 1 to 5 or the composition according to claim 6 or claim 7.
9. A nucleic acid molecule encoding the ATF5 peptide according to any one of claims 1 to 5.
10. Use of the ATF5 peptide according to any one of claims 1 to 5, the composition according to claim 6 or claim 7, or the nucleic acid according to claim 9 in the manufacture of a medicament for promoting cytotoxicity in a neoplastic cell.
11. Use of the ATF5 peptide according to any one of claims 1 to 5, the composition according to claim 6 or claim 7, or the nucleic acid according to claim 9 in the manufacture of a medicament for inhibiting proliferation of a neoplastic cell.
12. An ATF5 peptide according to any one of claims 1 to 5, substantially as herein described with reference to any one or more of the examples but excluding comparative examples.
13. A composition comprising an ATF5 peptide according to claim 6 or claim 7, substantially as herein described with reference to any one or more of the examples but excluding comparative examples.
14. A kit comprising an ATF5 peptide according to claim 8, substantially as herein described with reference to any one or more of the examples but excluding comparative examples.
15. A nucleic acid molecule according to claim 9, substantially as herein described with reference to any one or more of the examples but excluding comparative examples.
16. Use of an ATF5 peptide according to claim 10 or claim 11, substantially as herein described with reference to any one or more of the examples but excluding comparative examples.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201862613083P | 2018-01-03 | 2018-01-03 | |
| NZ765759A NZ765759A (en) | 2018-01-03 | 2019-01-03 | Atf5 peptide variants and uses thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ801728A NZ801728A (en) | 2024-03-22 |
| NZ801728B2 true NZ801728B2 (en) | 2024-06-25 |
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