Polypeptides of covalently linked synthetic bioactive peptide analog(s) for treatment of cancer
A polypeptide of the formula (I), P a -L-P b -L-P c -L-P d .
1. A polypeptide of the formula (I),
P a -L-P b -L-P c -L-P d ,
where,
P a , P b , P c , and P d represent any of the peptides P1, P2, P3 or P4 or a pharmaceutically acceptable salt thereof;
L is a linker used to link the peptides and is selected from the group consisting of lysine, lysine-lysine, lysine-arginine, arginine-lysine and arginine-arginine;
wherein,
P1 is Leu-Met-Tyr-Pro-Thr-Tyr-Leu-Lys (SEQ ID NO: 1)
P2 is D-Phe-Gln-Trp-Ala-Val-Aib-His-Leu (SEQ ID NO: 2)
P3 is D-Arg-Pro-Lys-Pro-D-Phe-Gln-D-Trp-Phe-D-Trp-Leu-Ac5c (SEQ ID NO: 3) and
P4 is D-Phe-Cys-Tyr-D-Trp-Orn-Ac5c-Pen-Thr, having a disulphide bond between Cys and Pen amino acids (SEQ ID NO: 4).
2. The polypeptide of the claim 1 , wherein P a is P4, P b is P3, P c is P1 and P d is P2; and said polypeptide is P4-Lys-Lys-P3-Lys-Lys-P1-Lys-P2 (SEQ ID NO:5).
3. The polypeptide of the claim 1 , wherein P a is P4, P b is P1, P c is P2 and P d is P3; and said polypeptide is P4-Lys-Lys-P1-Lys-P2-Lys-Lys-P3 (SEQ ID NO:6).
4. The polypeptide of the claim 1 , wherein P a is P3, P b is P2, P c is P1 and P d is P4; and said polypeptide is P3-Lys-Lys-P2-Lys-Lys-P1-Lys-P4 (SEQ ID NO:7).
5. The polypeptide of the claim 1 , wherein P a is P4, P b is P3, P c is P1 and P d is P2; and said polypeptide is P4-Lys-Arg-P3-Lys-Lys-P1-Lys-P2 (SEQ ID NO:8).
6. The polypeptide of the claim 1 , wherein P a is P4, P b is P3, P c is P1 and P d is P2; and said polypeptide is P4-Arg-Lys-P3-Arg-Lys-P1-Lys-P2 (SEQ ID NO:9).
7. The polypeptide of the claim 1 , wherein P a is P4, P b is P3, P c is P1 and P d is P2; and said polypeptide is P4-Arg-Arg-P3-Arg-Arg-P1-Lys-P2 (SEQ ID NO:10).
8. A composition comprising a polypeptide of formula (I),
P a -L-P b -L-P c -L-P d ,
where,
P a , P b , P c , and P d represent any of the peptides P1, P2, P3 or P4 or a pharmaceutically acceptable salt thereof;
L is a linker used to link the peptides and is selected from the group consisting of lysine, lysine-lysine, lysine-arginine, arginine-lysine and arginine-arginine,
wherein,
P1 is Leu-Met-Tyr-Pro-Thr-Tyr-Leu-Lys (SEQ ID NO: 1)
P2 is D-Phe-Gln-Trp-Ala-Val-Aib-His-Leu (SEQ ID NO: 2)
P3 is D-Arg-Pro-Lys-Pro-D-Phe-Gln-D-Trp-Phe-D-Trp-Leu-Ac5c (SEQ ID NO: 3) and
P4 is D-Phe-Cys-Tyr-D-Trp-Orn-Ac5c-Pen-Thr, having a disulphide bond between Cys and Pen amino acids (SEQ ID NO: 4) and a diluent, excipient, solvent, binder or stabilizer.
9. The composition according to claim 8 wherein the polypeptide is P4-Lys-Lys-P3-Lys-Lys-P1-Lys-P2 (SEQ ID NO:5).
10. The composition of claim 8 , wherein the polypeptide is P4-Lys-Lys-P1-Lys-P2-Lys-Lys-P3 (SEQ ID NO:6).
11. The composition of claim 8 , wherein the polypeptide is P3-Lys-Lys-P2-Lys-Lys-P1-Lys-P4 (SEQ ID NO:7).
12. The composition of claim 8 , wherein the polypeptide is P4-Lys-Arg-P3-Lys-Lys-P1-Lys-P2 (SEQ ID NO:8).
13. The composition of claim 8 , wherein the polypeptide is P4-Arg-Lys-P3-Arg-Lys-P1-Lys-P2 (SEQ ID NO:9).
14. The composition of claim 8 , wherein the polypeptide is P4-Arg-Arg-P3-Arg-Arg-P1-Lys-P2 (SEQ ID NO:10).
15. A method for treating cancer or a tumor comprising administering an effective amount of a polypeptide of the formula (I)
P a -L-P b -L-P c -L-P d ,
where,
P a , P b , P c , and P d represent any of the peptides P1, P2, P3 or P4 or a pharmaceutically acceptable salt thereof;
L is a linker used to link the peptides and is selected from the group consisting of lysine, lysine-lysine, lysine-arginine, arginine-lysine or arginine-arginine
wherein,
P1 is Leu-Met-Tyr-Pro-Thr-Tyr-Leu-Lys (SEQ ID NO: 1)
P2 is D-Phe-Gln-Trp-Ala-Val-Aib-His-Leu (SEQ ID NO: 2)
P3 is D-Arg-Pro-Lys-Pro-D-Phe-Gln-D-Trp-Leu-Ac5c (SEQ ID NO: 3) and
P4 is D-Phe-Cys-Tyr-D-Trp-Orn-Ac5c-Pen-Thr, having a disulphide bond between Cys and Pen amino acids (SEQ ID NO: 4).
16. The method of claim 15 , wherein P a is P4, P b is P3, P c is P1 and P d is P2; and the polypeptide is P4-Lys-Lys-P3-Lys-Lys-P1-Lys-P2 (SEQ ID NO:5).
17. The method of claim 15 , wherein P a is P4, P b is P1, P c is P2 and P d is P3; and the polypeptide is P4-Lys-Lys-P1-Lys-P2-Lys-Lys-P3 (SEQ ID NO:6).
18. The method of claim 15 , wherein P a is P3, P b is P2, P c is P1 and P d is P4; and the polypeptide is P3-Lys-Lys-P2-Lys-Lys-P1-Lys-P4 (SEQ ID NO:7).
19. The method of claim 15 , wherein P a is P4, P b is P3, P c is P1 and P d is P2; and the polypeptide is P4-Lys-Arg-P3-Lys-Arg-P1-Lys-P2 (SEQ ID NO:8).
20. The method of claim 15 , wherein P a is P4, P b is P3, P c is P1 and P d is P2; and the polypeptide is P4-Arg-Lys-P3-Arg-Lys-P1-Lys-P2 (SEQ ID NO:9).
21. The method of claim 15 , wherein P a is P4, P b is P3, P c is P1 and P d is P2; and the polypeptide is P4-Arg-Arg-P3-Arg-Arg-P1-Lys-P2 (SEQ ID NO:10).
22. The method according to claim 15 , wherein the cancer is oral, pancreatic, colon, lung, breast or leukemia.
23. The method of claim 16 , wherein the cancer is oral, pancreatic, colon, lung, breast or leukemia.
24. The method of claim 17 , wherein the cancer is oral, pancreatic, colon, lung, breast or leukemia.
25. The method according to claim 18 , wherein the cancer is oral, pancreatic, colon, lung, breast or leukemia.
26. The method of claim 19 , wherein the cancer is oral, pancreatic, colon, lung, breast or leukemia.
27. The method of claim 20 , wherein the cancer is oral, pancreatic, colon, lung, breast or leukemia.
28. The method according to claim 21 , wherein the cancer is oral, pancreatic, colon, lung, breast or leukemia.