Compositions and methods for inhibiting cellular adhesion or directing diagnostic or therapeutic agents to RGD binding sites
Compounds comprising R-G-Cysteic Acid (i.e., R-G-NH—CH(CH 2 —SO 3 H)COOH or Arg-Gly-NH—CH(CH 2 —SO 3 H)COOH) and derivatives thereof, including pharmaceutically acceptable salts, hydrates, stereoisomers, multimers, cyclic forms, linear forms, drug-conjugates, pro-drugs and their derivatives. Also disclosed are methods for making and using such compounds including methods for inhibiting cellular adhesion to RGD binding sites or delivering other diagnostic or therapeutic agents to RGD binding sites in human or animal subjects.
1. A method for inhibiting integrin-extracellular matrix interactions in a human or animal subject in need thereof, said method comprising the step of:
administering to the subject an effective amount of a cyclic or linear compound comprising either
i) a peptide which comprises Glycinyl-Arginyl-GlycinylCysteic-Threonyl-Proline-COOH or
ii) a peptide which has the formula:
X 1 —R - G -Cysteic Acid- X
where X and x1 are selected from: Phe-Val-Ala, -Phe-Leu-Ala, -Phe-Val-Gly, -Phe-Leu-Gly, -Phe-Pro-Gly, -Phe-Pro-Ala, -Phe-Val; or fromAru, Gly, Cysteic, Phe, Ala, Lea, Pro, Thr and salts thereof and any combinations of D-isomers and L-isomers thereof.
2. A method according to claim 1 wherein the compound comprises:
Glycinyl-Arginyl-Glycinyl-Cysteic-Threonyl-Proline-COOH.
3. A method according to claim 2 wherein the compound has the formula:
4. A method according to claim 2 wherein the compound is linear.
5. A method according to claim 2 wherein the compound is cyclic.
6. A method according to claim 1 wherein the method is carried out to treat an eye disorder.
7. A method according to claim 6 wherein the method is carried out to treat a disorder selected from; neovascularization, neovascular glaucoma, diabetic retinopathy, retinal degeneration, dry macular degeneration, wet macular degeneration, corneal neovascularization, edematous sclerosis, corneal graft neovascularization, neovascular glaucoma, diabetic retinopathy, pterygium retinal degeneration, dry and wet macular degeneration, conical neovascularization, ischemic optic nerve, rubiosis iridis, central vein occlusion, aberrant epiretinal membranes, retrolental fibroplasia, granular conjunctivitis.
8. A method according to claim 6 wherein the administration is topical.
9. A method according to claim 6 wherein the administration is intraocular.
10. A method according to claim 6 wherein the administration is intravitreal.