Compounds and methods of modulating angiogenesis
A method of modulating angiogenesis in a tissue comprises administering to the tissue a therapeutically effective amount of an agent that modulates complex formation of α v β 3 integrin and VEGFR2.
1. A method of inhibiting complexing of αυβ3 integrin and VEGFR2 in a cell population, the method comprising contacting the cell population including cells that express α v β 3 integrin and VEGFR2 with a therapeutically effective amount of a peptide that inhibits complexing α v β 3 integrin and VEGFR2, wherein the peptide consisting of the amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 4, and SEQ ID NO: 5.
2. The method of claim 1 , wherein the peptide inhibiting tyrosine phosphorylation of at least one of the expressed α v β 3 integrin and VEGFR2.
3. The method of claim 1 , wherein the peptide does not inhibiting natural ligand binding to the α v β 3 integrin.
4. The method of claim 1 , wherein the peptide inhibiting tyrosine phosphorylation of the α v β 3 integrin.
5. The method of claim 1 , wherein the peptide inhibiting tyrosine phosphorylation of VEGFR2 upon VEGF stimulation.
6. The method of claim 1 , wherein the peptide competing with α v β 3 integrin for interaction with VEGFR2.
7. The method of claim 1 , wherein the peptide comprising a phosphorylated tyrosine residue and the peptide corresponding to a portion of the cytoplasmic domain of at least one of α v β 3 integrin.
8. The method of claim 7 , wherein the peptide containing a tyrosine residue, which is capable of being phosphorylated upon complex formation of the α v β 3 integrin and VEGFR2.
9. The method of claim 1 , wherein the cells comprising at least one of tumor cells or endothelial cells.
10. A method of treating aberrant angiogenesis in a tissue, the method comprising administering to the tissue a therapeutically effective amount of a peptide that inhibits complex formation of α v β 3 integrin and VEGFR2, wherein the peptide consisting of the amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 4, and SEQ ID NO: 5.
11. The method of claim 10 , wherein the peptide does not inhibiting natural ligand binding to the α v β 3 integrin.
12. The method of claim 10 , wherein the peptide inhibiting phosphorylation of the α v β 3 integrin.
13. The method of claim 10 , wherein the peptide inhibiting phosphorylation of VEGFR2 upon VEGF stimulation.
14. The method of claim 10 , wherein the peptide competing with α v β 3 integrin for interaction with VEGFR2.
15. The method of claim 10 , wherein the peptide comprising a phosphorylated tyrosine residue and the peptide sequence corresponding to a portion of the cytoplasmic domain of at least one of α v β 3 integrin or.
16. The method of claim 15 , wherein the peptide containing a tyrosine residue which is capable of being phosphorylated upon complex formation of the α v β 3 integrin and VEGFR2.
17. The method of claim 10 , wherein the cells comprising at least one of tumor cells or endothelial cells.
18. A method of treating an angiogenic disorder in a subject, comprising:
administering to cells of the subject expressing α v β 3 integrin and VEGFR2 a therapeutically effective amount of peptide that inhibits complexing of α v β 3 integrin and VEGFR2, wherein the peptide consisting of the amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 4, and SEQ ID NO: 5.
19. The method of claim 18 , wherein the peptide does not inhibiting natural ligand binding to the α v β 3 integrin.
20. The method of claim 18 , wherein the peptide inhibiting tyrosine phosphorylation of the α v β 3 integrin.
21. The method of claim 18 , wherein the peptide inhibiting tyrosine phosphorylation of VEGFR2 upon VEGF stimulation.
22. The method of claim 18 , wherein the peptide competing with α v β 3 integrin for interaction with VEGFR2.
23. The method of claim 18 , wherein the peptide comprising a phosphorylated tyrosine residue and the peptide corresponding to a portion of the cytoplasmic domain of at least one of α v β 3 integrin or.
24. The method of claim 18 , wherein the peptide containing a tyrosine residue, which is capable of being phosphorylated upon complex formation of the α v β 3 integrin and VEGFR2.
25. The method of claim 18 , wherein the angiogenic disorder is aberrant tumor growth.
26. The method of claim 18 , wherein the angiogenic disorder is age-related macular degeneration.