Compositions and methods for inhibiting cellular adhesion or directing diagnostic or therapeutic agents to RGD binding sites
AssigneeAllegro Pharmaceuticals, LLC
InventorsMichael John Mackel, John Park
Life of this patent
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Abstract
Compounds comprising R-G-Cysteic Acid (i.e., R-G-NH—CH(CH2—SO3H)COOH or Arg-Gly-NH—CH(CH2—SO3H)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.
Claims27
A method of inhibiting adhesion of cells to RGD binding sites comprising administering to a subject in need thereof an effective amount of a cyclic or linear compound comprising either:
- i) a peptide which comprises Glycinyl-Arginyl-Glycinyl-Cysteic-Threonyl-Proline-COOH or
- ii) a peptide which has the formula:
- X1—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 from Arg, Gly, Cysteic, Phe, Val, Ala, Leu, Pro, Thr and salts thereof and any combinations of D-isomers and L-isomers thereof.
A method of antagonizing an RGD-binding integrin in a subject comprising administering to a subject in need thereof an effective amount of a cyclic or linear compound comprising either:
- i) a peptide which comprises Glycinyl-Arginyl-Glycinyl-Cysteic-Threonyl-Proline-COOH or
- ii) a peptide which has the formula:
- X1—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 from Arg, Gly, Cysteic, Phe, Val, Ala, Leu, Pro, Thr and salts thereof and any combinations of D-isomers and L-isomers thereof.
A method of antagonizing an integrin in a subject comprising administering to a subject in need thereof a cyclic or linear compound comprising either:
- i) a peptide which comprises Glycinyl-Arginyl-Glycinyl-Cysteic-Threonyl-Proline-COOH or
- ii) a peptide which has the formula:
- X1—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 from Arg, Gly, Cysteic, Phe, Val, Ala, Leu, Pro, Thr and salts thereof and any combinations of D-isomers and L-isomers thereof, wherein said integrin is one which is subject to antagonism by an RGD peptide.
Dependencies are inferred from the claim text.