CS-1 peptidomimetics, compositions and methods of using the same

Details CS-1 peptidomimetics, compositions and methods of using the same CS-1 peptidomimetics, compositions and methods of using the same

1995-05-05

1997-11-18

Tsang, Cecilia J.

Chemistry: natural resins or derivatives; peptides or proteins;

Peptides of 3 to 100 amino acid residues

4 to 5 amino acid residues in defined sequence

514 18, 514 19, 514 17, 530331, A61K 3807

Patent

active

056889135

ABSTRACT:
The present invention contemplates a peptide that inhibits the binding between the VLA-4 receptor expressed on inflammatory leukocytes and the fibronectin CS-1 peptide expressed on endothelial cells that are involved in immunoinflammatory disease states. Pharmaceutical compositions containing a contemplated peptide and processes for treating immunoinflammatory conditions using a binding-inhibitory peptide are also disclosed.

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Komoriya, Akira et al., "The Minimal Essential Sequence for a Major Cell Type-specific Adhesion Site (CS1) within the Alternatively Splice Type III Connecting Segment Domain of Fibronectin is Leucine-Asparatic Acid-Valine." J. Biol. Chem. 266:15075-15079 (1991).
Elices, Mariano "The Integrin .alpha..sub.4 .beta..sub.1 (VLA-4) as a Therapeutic Target." Cell Adhesion and Human Disease. Wiley, Chichester (Ciba Foundation Symposium 189) pp. 79-90 (1995).
Nowlin, Dawn M., "A Novel Cyclic Pentapeptide Inhibits .alpha.4.beta.1 and .alpha.5.beta.1 Integrin-mediated Cell Adhesion." J. Biol. Chem. 268:20352-20359 (1993).
Mousa, Shaker A. et al., "Antiplatelet Efficacy and Specificity of DMP728, a Novel Platelet GP11b/IIIa Receptor Antagonist." Clin. Pharm. 83:374-382 (1993).
Cardarelli, Pina M. et al., "Cyclic RGD Peptide Inhibits .alpha.4.beta.1 Interaction with Connecting Segment 1 and Vascular Cell Adhesion Molecule." J. Biol. Chem. 269:18668-18673 (1994).
Pfaff, Martin et al., "Selective Recognition of Cyclic RGD Peptides of NMR Defined Conformation by .alpha.V.beta.3, .alpha.5.beta.1 Integrins." J. Biol. Chem. 269:20233-20238 (1994).
Esser et al. "N-terminale Cyclisierung Von Peptiden mit N, N' Carbonyldimidazole oder N, N'-thiocarbonyldimidazol"Agnew. Chem. 90(6):495-496 (1978).
Esser, F. and Roos, O. "N-terminal Cyclization of Peptides with N, N'-Carbonyldiimidazole or N,N'-Thiocarbonyldiimidazole"Agnew. Chem. Int. Ed. Engl. 17(6):467-468 (1978).
Iorio et al., J. Med. Chem., 1991, vol. 34, pp. 2615-2623.

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