Peptides for the treatment of malignant proliferative diseases

1. A peptide of 9-15 amino acids comprising the sequence Lys-Gly-His-Tyr-X 1 -X 2 -X 3 -Val-Gly (SEQ ID NO: 6), wherein X 1 -X 2 -X 3 represents a sequence selected from the group consisting of Ala-Glu-Arg(Z), Ala-Arg(Z)-Glu and Arg(Z)-Ala-Glu, wherein Z is selected from the group consisting of Pbf (2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl) and Nitro (NO 2 ), wherein the peptide is at least 95% pure.

2. The peptide of claim 1 , comprising the sequence selected from the group consisting of:

(SEQ ID NO: 1)

Lys-Gly-His-Tyr-Ala-Glu-Arg(Pbf)-Val-Gly;

(SEQ ID NO: 2)

Lys-Gly-His-Tyr-Arg(Pbf)-Ala-Glu-Val-Gly;

and

(SEQ ID NO: 4)

Lys-Gly-His-Tyr-Ala-Glu-Arg(NO 2 )-Val-Gly.

3. The peptide of claim 1 , further comprising at least one modification selected from the group consisting of an amino-terminal modification and a carboxy-terminal modification.

4. The peptide of claim 1 , wherein the peptide is of 9-12 amino acids.

5. The peptide of claim 1 , wherein the peptide is of 9 amino acids.

6. The peptide of claim 1 , selected from the group consisting of:

(SEQ ID NO: 7)

R 1 -Lys-Gly-His-Tyr-Ala-Glu-Arg(Pbf)-Val-Gly-R 2 ;

(SEQ ID NO: 8)

R 1 -Lys-Gly-His-Tyr-Arg(Pbf)-Ala-Glu-Val-Gly-R 2 ;

and

(SEQ ID NO: 9)

R 1 -Lys-Gly-His-Tyr-Ala-Glu-Arg(NO 2 )-Val-Gly-R 2 ,

wherein R 1 designates a hydrogen of an unmodified amino terminal group or is an amino blocking group selected from the group consisting of acyl and alkyl; and R 2 designates OH of an unmodified carboxy terminal group or is a carboxyl blocking group selected from the group consisting of an amide, alcohol and ester.

7. The peptide of claim 1 , selected from the group consisting of:

(SEQ ID NO: 1)

H-Lys-Gly-His-Tyr-Ala-Glu-Arg(Pbf)-Val-Gly-OH;

(SEQ ID NO: 2)

H-Lys-Gly-His-Tyr-Arg(Pbf)-Ala-Glu-Val-Gly-OH;

and

(SEQ ID NO: 4)

H-Lys-Gly-His-Tyr-Ala-Glu-Arg(NO 2 )-Val-Gly-OH.

8. A conjugate comprising the peptide of claim 1 and a moiety selected from the group consisting of a permeability enhancing moiety, a targeting moiety and a carrier moiety.

9. A pharmaceutical composition comprising the peptide of claim 1 and a pharmaceutically acceptable carrier, excipient or diluent.

10. A method for inhibiting cancer cell growth and metastasis in a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of the peptide of claim 1 .

11. The method of claim 10 , wherein the cancer is a solid tumor.

12. The method of claim 11 , wherein the solid tumor is selected from the group consisting of lung cancer, colon cancer, breast cancer, pancreatic cancer, prostate cancer, melanoma, and ovarian cancer.

13. The method of claim 10 , wherein the cancer is a non-solid malignant disease.

14. A peptide selected from the group consisting of:

(SEQ ID NO: 10)

R 1 -Lys-Gly-His-Tyr-Ala-Glu-Arg(Z)-Val-Gly-R 2 ;

(SEQ ID NO: 11)

R 1 -Lys-Gly-His-Tyr-Ala-Arg(Z)-Glu-Val-Gly-R 2 ;

(SEQ ID NO: 12)

R 1 -Lys-Gly-His-Tyr-Arg(Z)-Ala-Glu-Val-Gly-R 2 ;

(SEQ ID NO: 13)

R 1 -Lys-Gly-His-Arg(Z)-Tyr-Ala-Glu-Val-Gly-R 2 ;

(SEQ ID NO: 14)

R 1 -Lys-Gly-Arg(Z)-His-Tyr-Ala-Glu-Val-Gly-R 2 ;

(SEQ ID NO: 15)

R 1 -Lys-Arg(Z)-Gly-His-Tyr-Ala-Glu-Val-Gly-R 2 ;

and

(SEQ ID NO: 16)

R 1 -Lys-Gly-His-Tyr-Ala-Glu-Val-Arg(Z)-Gly-R 2 ;

wherein:

R 1 designates a hydrogen of an unmodified amino terminal group or is selected from the group consisting of: (i) an amino blocking group selected from acyl and alkyl, and (ii) a permeability-enhancing or targeting moiety;

R 2 designates OH of an unmodified carboxy terminal group or is selected from the group consisting of: (i) a carboxyl blocking group selected from the group consisting of an amide, alcohol and ester, and (ii) a permeability-enhancing or targeting moiety; and

Z is selected from the group consisting of Pbf (2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl) and Nitro (NO 2 ), wherein the peptide is at least 95% pure.

15. The peptide of claim 14 , wherein the peptide is conjugated to a moiety selected from the group consisting of a fatty acid, a synthetic polymer, a carrier or targeting peptide, a carrier or targeting protein, and a sugar moiety.

16. A pharmaceutical composition comprising the peptide of claim 14 and a pharmaceutically acceptable carrier, excipient or diluent.

17. A method for inhibiting cancer cell growth and metastasis in a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of the peptide of claim 14 .

18. The method of claim 17 , wherein the cancer is a solid tumor.

19. The method of claim 18 , wherein the solid tumor is selected from the group consisting of lung cancer, colon cancer, breast cancer, pancreatic cancer, prostate cancer, melanoma, and ovarian cancer.

20. The method of claim 17 , wherein the cancer is a non-solid malignant disease.