Protein interfaces

• US 10,188,691 B2
• Filed: 08/22/2017
• Issued: 01/29/2019
• Est. Priority Date: 05/27/2016
• Status: Active Grant

• Current Assignee: SyntheX, Inc.
• Original Assignee: SyntheX, Inc.
• Inventors: Chahwan, Charly, Soloveychik, Maria
• Primary Examiner(s): Alstrum-Acevedo, James H
• Assistant Examiner(s): Martinez, Tara L
• Application Number:
  US15/683,586
• Publication Number:
  US 20170368132A1
• Time in Patent Office: 525 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/585 wherein the target is cancer
• 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: A61K 38/02 Peptides of undefined number of amino acids; Derivatives thereof
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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: C07K 14/00 Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
• CPC Class Codes: C07K 16/30 from tumour cells
• CPC Class Codes: C07K 5/1019 with the first amino acid being basic
• CPC Class Codes: C07K 7/06 having 5 to 11 amino acids
• CPC Class Codes: C07K 7/08 having 12 to 20 amino acids gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68
• CPC Class Codes: C12N 15/1055 Protein x Protein interaction, e.g. two hybrid selection
• CPC Class Codes: C12N 15/81 for yeasts
• CPC Class Codes: G01N 33/5023 on expression patterns
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present disclosure provides methods to treat conditions, including cancer, using compounds that can target resistant cancer cells. The compounds can be used to sensitize resistant cancer cells or decrease the proliferation of cells. The compounds can target proteins in the DNA damage repair pathway leading to a decrease in DNA damage repair in target cells.

Claims

1. A non-naturally occurring peptide of fewer than 30 amino acid residues which interacts with RAD51 Associated Protein 1′

s (RAD51AP1′

s) binding site on human RAD51 recombinase (RAD51), wherein the non-naturally occurring peptide consists of the amino acid sequence of SEQ ID NO;

1, SEQ ID NO;

5, SEQ ID NO;

10, SEQ ID NO;

66, or SEQ ID NO;

67, wherein any of the amino acids are optionally D-amino acids.

2. The non-naturally occurring peptide of claim 1, wherein the polypeptide comprises both (L)- and (D)-amino acids.

3. The non-naturally occurring peptide of claim 1, wherein the polypeptide comprises at least one (D)-amino acid.

4. The non-naturally occurring peptide of claim 1, wherein the polypeptide does not comprise any (L)-amino acids.

5. The non-naturally occurring peptide of claim 1, consisting of the amino acid sequence of SEQ ID NO.:

1, wherein any of the amino acids are optionally D-amino acids.

6. The non-naturally occurring peptide of claim 1, consisting of the amino acid sequence of SEQ ID NO.:

5, wherein any of the amino acids are optionally D-amino acids.

7. The non-naturally occurring peptide of claim 1, consisting of the amino acid sequence of SEQ ID NO.:

10, wherein any of the amino acids are optionally D-amino acids.

8. The non-naturally occurring peptide of claim 1, consisting of the amino acid sequence of SEQ ID NO.:

66, wherein any of the amino acids are optionally D-amino acids.

9. The non-naturally occurring peptide of claim 1, consisting of the amino acid sequence of SEQ ID NO.:

67, wherein any of the amino acids are optionally D-amino acids.

10. A pharmaceutical composition, comprising the non-naturally occurring peptide of claim 1 and a pharmaceutically-acceptable excipient.

11. A method of inducing cell death, the method comprising contacting a cell with the peptide of claim 1.

12. The method of claim 11, wherein the peptide binds to RAD51 in a cell, wherein the binding of the polypeptide to the eukaryotic recombinase inhibits binding of RAD51 to a protein in the cell, wherein the cell exhibits an increase in intracellular free calcium concentration upon binding of the polypeptide to RAD51.