Mimetic peptides derived from collagen type IV and their use for treating angiogenesis- and lymphangiogenesis-dependent diseases
Mimetic peptides having anti-angiogenic and anti-tumorigenic properties and methods of their use for treating cancer, ocular diseases, such as age-related macular degeneration, and other-angiogenesis-dependent diseases are disclosed. More particularly, active non-cysteine analogs (mimetics), which exhibit anti-angiogenic activity in endothelial cell proliferation, migration, adhesion, and tube formation assays, anti-migratory activity in human breast cancer cells in vitro, anti-angiogenic and anti-tumori-genic activity in vivo in breast cancer xenograft models, and age-related macular degeneration models are disclosed. The presently disclosed mimetic peptides also exhibit anti-lymphangiogenic and directly anti-tumorigenic properties.
1. A method for treating ocular angiogenesis or ocular vascular permeability not associated with cancer in a patient, comprising administering to the patient an effective amount of a peptide having the amino acid sequence of LRRFSTXPXXXXNINNVXNF (SEQ ID NO: 1), and having at least 85% identity to the amino acid sequence LRRFSTAPFAFININNVINF (SEC) ID NO: 17), optionally having one or more D amino acids.
2. The method of claim 1 , wherein X at position 12 and position 18 are hydrophobic amino acids.
3. The method of claim 1 , wherein X at position 12 and position 18 is I or A.
4. The method of claim 1 , wherein X at position 7 and position 10 are not methionine.
5. The method of claim 1 , wherein X at position 10 is A or dA.
6. The method of claim 1 , wherein X at position 10 is A.
7. The method of claim 1 , wherein X at position 7 is M, A, or G; X at position 9 is F, A, Y, or G; X at position 10 is M, A, G, dA, or Nle; X at position 11 is F, A, Y, G, or 4-ClPhe; X at position 12 and position 18 are G, V, T, I, L or AllyGly.
8. The method of claim 1 , wherein the peptide comprises an amino acid sequence selected from: (SEQ ID No: 11) LRRFSTMPFMFININNVINF: (SEQ ID No: 15) LRRFSTMPFdAFININNVINF: and (SEQ ID No: 16) LRRFSTAPFMFININNVINF.
9. The method of claim 1 , wherein the peptide is administered as a pharmaceutical composition comprising the effective amount of the peptide and a pharmaceutically acceptable carrier.
10. The method of claim 9 , wherein the pharmaceutical composition is administered locally or systemically.
11. The method of claim 10 , wherein the pharmaceutical composition is formulated for parenteral delivery.
12. The method of claim 10 , wherein the pharmaceutical composition is administered by intraocular delivery.
13. The method of claim 1 , wherein the patient has age-related macular degeneration.
14. The method of claim 1 , wherein the patient has macular edema.
15. The method of claim 1 , wherein the patient has neovascular glaucoma.
16. The method of claim 1 , wherein the patient has proliferative diabetic retinopathy.
17. The method of claim 1 , wherein the patient has retinopathy of prematurity.
18. The method of claim 1 , wherein the peptide has at least 90% identity to the amino acid sequence of SEQ ID NO: 17.