Inhibiting interaction between the HIF-1ALPHA and p300/CBP with hydrogen bond surrogate-based helices

• US 9,399,666 B2
• Filed: 09/18/2009
• Issued: 07/26/2016
• Est. Priority Date: 09/18/2008
• Status: Active Grant

• Current Assignee: New York University, Arizona Board of Regents (University of Arizona)
• Original Assignee: New York University, Arizona Board of Regents (University of Arizona)
• Inventors: Arora, Paramjit S., Olenyuk, Bogdan, Chapman, Ross N., Henchey, Laura, Block, Katherine M.
• Primary Examiner(s): Audet, Maury
• Assistant Examiner(s): REYNOLDS, FRED H
• Application Number:
  US13/119,108
• Publication Number:
  US 20110245175A1
• Time in Patent Office: 2,503 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: C07K 14/4702 Regulators; Modulating activity
• CPC Class Codes: C07K 7/04 Linear peptides containing only normal peptide links
• CPC Class Codes: G01N 2500/02 Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor)

Abstract

The present invention relates to peptides having one or more stable, internally constrained α-helices, and that include a sequence that mimics at least a portion of the C-terminal transactivation domain of HIF-1α. Also disclosed are pharmaceutical compositions containing these peptides and methods of using these peptides, for example to reduce gene transcription, treat or prevent disorders mediated by interaction of HIF-1α with CREB-binding protein and/or p300, reduce or prevent angiogenesis in a tissue, induce apoptosis, decrease cell survival and/or proliferation, and identify potential ligands of CREB-binding protein and/or p300.

Claims

1. A peptide of formula I:

2. The peptide according to claim 1, wherein the peptide is selected from the group consisting of:

3. A pharmaceutical composition comprising a peptide according to claim 1 and a pharmaceutically acceptable vehicle.

4. The peptide according to claim 1, wherein each n is 1.

5. The peptide according to claim 1, wherein one n is 1 and one n is 2.

6. The peptide according to claim 1, wherein each n is 2.