p53 activating peptides

Patent metadata

Field	Value
Publication number	US-9517252-B2
Application number	US-201214350390-A
Country	US
Kind code	B2
Filing date	Sep 10, 2012
Priority date	Sep 9, 2011
Publication date	Dec 13, 2016
Grant date	Dec 13, 2016

Abstract

The present invention is directed to p53 activating peptides. The present further describes methods for generating these peptides and the use of these peptides.

First claim

The invention claimed is:

1. A peptide capable of restoring the sequence-specific DNA binding or transactivation function of a mutant p53, wherein the peptide:
(a) comprises a sequence selected from the group consisting of:

(SEQ ID NO: 55)

S P T T N H

(SEQ ID NO: 56)

M P H L M A C

(SEQ ID NO: 57)

T A L I D I W E H S V L G K G Y P R M S

(SEQ ID NO: 58)

I L N V L P L L A S R K P

(SEQ ID NO: 59)

VSWSACVLLELCNYFPENPIEEEDWACLG

(SEQ ID NO: 60)

R L Q Q V

(SEQ ID NO: 61)

V R H Q H V G A T I L G W K

(SEQ ID NO: 62)

V R H Q H V G A T I L G W KMGWTDH

(SEQ ID NO: 63)

MS P T T N H

(SEQ ID NO: 64)

MM P H L M A C

(SEQ ID NO: 65)

MT A L I D I W E H S V L G K G Y P R M S

(SEQ ID NO: 66)

MI L N V L P L L A S R K P

(SEQ ID NO: 67)

MVSWSACVLLELCNYFPENPIEEEDWACLG

(SEQ ID NO: 68)

MR L Q Q V

(SEQ ID NO: 69)

MV R H Q H V G A T I L G W K

(SEQ ID NO: 70)

MV R H Q H V G A T I L G W KMGWTDH

MLM

(SEQ ID NO: 71)

TTLIDIWEHSVLGKGYPRMS

(SEQ ID NO: 72)

M TTLIDIWEHSVLGKGYPRMS

(SEQ ID NO: 73)

RAVTDRPVPCPNPRLNLVAN

(SEQ ID NO: 74)

M RAVTDRPVPCPNPRLNLVAN

(b) is a variant of a peptide as defined in (a) above; or
(c) is a derivative of a peptide as defined in (a) or (b) above.

2. The peptide which is a variant according to claim 1 (b), wherein the variant is a fragment of a peptide as defined in claim 1 (a).

3. The peptide which is a derivative according to claim 1 (c), wherein the derivative is a peptide which has undergone a post-translational modification.

4. The peptide according to claim 1 wherein the peptide is fused to a heterologous polypeptide sequence.

5. The peptide according to claim 1 wherein the peptide is a stably cross-linked peptide (a “stapled” peptide) wherein the cross-linked peptides contain at least two modified amino acids that together form an internal cross-link.

6. The peptide according to claim 1 wherein the mutant p53 is selected from the group consisting of: p53 G245S mutant, p53 R273H mutant p53 R248Q mutant the p53 R175H mutant.

7. An isolated nucleic acid molecule encoding a peptide according to claim 1 .

8. A vector comprising an isolated nucleic acid molecule according to claim 7 .

9. A pharmaceutical composition comprising a peptide according to claim 1 , an isolated nucleic acid molecule according to claim 7 , or a vector according to claim 8 , wherein the pharmaceutical composition optionally comprises one or more pharmaceutically acceptable excipients, vehicles or carriers.

10. The pharmaceutical composition according to claim 9 wherein the pharmaceutical composition comprises a further therapeutic compound, for example an anti-cancer agent.

11. The peptide according to claim 1 , an isolated nucleic acid molecule according to claim 7 or a vector according to claim 8 for use in medicine.

12. A method for obtaining a peptide which restores the sequence-specific DNA binding of a mut

Assignees

• Goh Walter
• Ghadessy Farid John
• Agency Science Tech & Res

Inventors

• Goh Walter
• Ghadessy Farid John

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K38/00

  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 title

• C12N15/1058

  Directional evolution of libraries, e.g. evolution of libraries is achieved by mutagenesis and screening or selection of mixed population of organisms · CPC title

• A61K38/08 Primary

  Peptides having 5 to 11 amino acids {(A61K38/043 - A61K38/046 take precedence)} · CPC title

• C07K7/08

  having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68) · CPC title