Anti-angiogenic molecules, nanostructures and uses thereof
The disclosure is generally directed toward the design and synthesis of peptide amphiphile (PA) molecules that comprises a peptide configured to inhibit angiogenesis. The peptide amphiphile comprises a hydrophobic tail, peptide sequence capable of beta-sheet formation; and a peptide, wherein the peptide is configured to inhibit angiogenesis. Optionally the PA further comprises a flexible linker between the peptide sequence capable of beta-sheet formation and the peptides. Further this disclosure is directed to nanostructures comprising peptide amphiphiles configured to inhibit angiogenesis.
1. A composition, the composition comprising: (a) a hydrophobic tail; (b) a peptide sequence capable of beta-sheet formation; (c) a flexible peptide linker; and (d) a peptide configured to inhibit angiogenesis.
2. The composition as in claim 1 , wherein the flexible linker comprises GG.
3. The composition as in claim 1 , wherein the hydrophobic tail is a C6-C22 alkyl group.
4. The composition as in claim 1 , wherein the peptide sequence capable of beta-sheet formation comprises VVAA (SEQ ID NO: 19).
5. The composition as in claim 1 , wherein the peptide configured to inhibit angiogenesis comprises a PPPXHPPHPPP (SEQ ID NO: 20) sequence of amino acids, wherein P is a polar amino acid, H is an apolar amino acid and X is a glycine.
6. The composition as in claim 1 , wherein the peptide configured to inhibit angiogenesis comprises a maspin g-helix.
7. The composition as in claim 1 , wherein the peptide comprises ESTGLEKIEKQ (SEQ ID NO: 1).
8. The composition as in claim 1 , wherein the peptide comprises EDESTGLEKIEKQLN (SEQ ID NO: 2).
9. A nanostructure, comprising the composition of claim 1 and further comprising a second peptide amphiphile.
10. A method of inhibiting angiogenesis, comprising contacting endothelial cells with the composition as in claim 1 in an amount effective to inhibit angiogenesis.
11. A composition, the composition comprising: (a) a hydrophobic tail; (b) a peptide sequence comprising VA and capable of beta-sheet formation; and (c) a peptide configured to inhibit angiogenesis.
12. The composition as in claim 11 , wherein the peptide sequence capable of beta-sheet formation comprises VVAA (SEQ ID NO: 19).
13. The composition as in claim 11 , further comprising a flexible linker between the peptide sequence comprising VA and capable of beta-sheet formation and the peptide configured to inhibit angiogenesis.
14. The composition as in claim 13 , wherein the flexible linker comprises GG.
15. The composition as in claim 11 , wherein the hydrophobic tail is a C6-C22 alkyl group.
16. The composition as in claim 11 , wherein the peptide configured to inhibit angiogenesis comprises a PPPXHPPHPPP (SEQ ID NO: 20) sequence of amino acids, wherein P is a polar amino acid, H is an apolar amino acid and X is a glycine.
17. The composition as in claim 11 , wherein the peptide configured to inhibit angiogenesis comprises a maspin g-helix.
18. The composition as in claim 11 , wherein the peptide comprises ESTGLEKIEKQ (SEQ ID NO: 1).
19. The composition as in claim 11 , wherein the peptide comprises EDESTGLEKIEKQLN (SEQ ID NO: 2).
20. A nanostructure, comprising the composition of claim 11 and further comprising a second peptide amphiphile.
21. A method of inhibiting angiogenesis, comprising contacting endothelial cells with the composition as in claim 11 in an amount effective to inhibit angiogenesis.