Peptides of syndecan-1 for inhibiting angiogenesis
The present invention provides a peptide derived from the extracellular domain of syndecan-1 that inhibits angiogenesis.
1. A method of treating a subject having a disease characterized by angiogenesis wherein the disease is not cancer, comprising contacting endothelial cells of the subject that express α V β 3 or α V β 5 integrin and are responsible for said angiogenesis with a peptide or polypeptide segment consisting of 32 to 100 amino acid residues and comprising SEQ ID NO:21, whereby the disease is treated.
2. The method of claim 1 , wherein said peptide or polypeptide segment is 35, 40, 45, 49, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 100 amino acid residues in length.
3. The method of claim 1 , wherein said peptide or polypeptide segment is 32 to 80 amino acid residues in length.
4. The method of claim 1 , wherein said peptide or polypeptide segment is 32 to 50 amino acid residues in length.
5. The method of claim 1 , wherein said peptide or polypeptide segment is 32 to 40 amino acid residues in length.
6. The method of claim 1 , wherein said peptide segment consists of SEQ ID NO:10.
7. The method of claim 1 , wherein said peptide segment comprises at least 35 contiguous amino acids from SEQ ID NO:10.
8. The method of claim 1 , wherein said peptide segment consists of SEQ ID NO:28.
9. The method of claim 1 , wherein said peptide segment consists of SEQ ID NO:21.
10. The method of claim 1 , wherein said disease is selected from the group consisting of abnormalities of the vasculature, abnormalities of the eye, abnormalities of the skin, abnormalities of the uterus and ovary, abnormalities of the adipose tissue, abnormalities of the bones and joints, and AIDS-related pathologies resulting from TAT protein of the human immunodeficiency virus (HIV) activating the α V β 3 integrin on endothelial cells.
11. The method of claim 10 , wherein said disease is selected from the group consisting of atherosclerosis, hemangiomas, diabetic retinopathy, retinopathy of prematurity, pyogenic granulomas, psoriasis, warts, scar keloids, allergic edema, ulcers, dysfunctional uterine bleeding, follicular cysts, endometriosis, pre-eclampsia, obesity, rheumatoid arthritis, and osteophyte formation.
12. The method of claim 1 , wherein contacting comprises systemic administration of said peptide or polypeptide segment or administration of said peptide or polypeptide segment local to said endothelial cells.
13. The method of claim 1 , wherein said peptide or polypeptide segment is active at 0.3 μM.
14. The method of claim 1 , wherein said peptide or polypeptide segment is active at 0.1 μM.
15. The method of claim 1 , further comprising contacting said endothelial cells with a second anti-angiogenic agent.