Stabilized p53 peptides and uses thereof

• US 9,527,896 B2
• Filed: 09/11/2014
• Issued: 12/27/2016
• Est. Priority Date: 01/31/2007
• Status: Active Grant

• Current Assignee: Dana-Farber Cancer Institute, President and Fellows of Harvard College (Harvard Corporation)
• Original Assignee: Dana-Farber Cancer Institute, President and Fellows of Harvard College (Harvard Corporation)
• Inventors: Bernal, Federico, Walensky, Loren D., Verdine, Gregory L., Korsmeyer, Stanley J.
• Primary Examiner(s): GUDIBANDE, SATYANARAYAN R
• Application Number:
  US14/483,905
• Publication Number:
  US 20150119551A1
• Time in Patent Office: 838 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 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: C07K 1/113 without change of the primary structure
• CPC Class Codes: C07K 14/4746 p53

Abstract

Cross-linked peptides related to human p53 and bind to HMD2 or a family member of HDM2 useful for promoting apoptosis, e.g., in the treatment of and identifying therapeutic agents that binding to HMD2 or a family member of HDM2.

Claims

1. A peptide of Formula (I),

2. The peptide of claim 1, wherein the peptide binds to HDM2.

3. The peptide of claim 1, wherein each R₃ is independently an alkenylene group.

4. The peptide of claim 1, wherein each R₃ is independently an alkylene group.

5. The peptide of claim 1, wherein each R₁ and each R₂ is independently alkyl.

6. The peptide of claim 1, wherein each R₁ and each R₂ is methyl.

7. The peptide of claim 1, wherein each R₁ and each R₂ is H.

8. The peptide of claim 1, wherein z is 1.

9. The peptide of claim 1, wherein each w is independently an integer from 3 to 15.

10. The peptide of claim 1, wherein each y is independently an integer from 3 to 15.

11. The peptide of claim 1, wherein the peptide is permeable to a cell membrane.

12. The peptide of claim 1, wherein the peptide comprises a helix.

13. The peptide of claim 1, wherein the peptide comprises an α

-helix.

14. The peptide of claim 13, wherein R₃ extends across the length of one helical turn.

15. The peptide of claim 13, wherein R₃ extends across the length of two helical turns.