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

Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – Tripeptides – e.g. – tripeptide thyroliberin – etc.

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Details

530330, 514 17, 514 18, 514 19, C07K 508

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active

059360658

ABSTRACT:
The present invention contemplates a compound defined by the following formula: ##STR1## that inhibits the binding between the VLA-4 and the fibronectin CS-1 compound. Pharmaceutical compositions containing a contemplated compound and methods for treating immunoinflammatory conditions using the compound are also disclosed.

REFERENCES:
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patent: 5387504 (1995-02-01), Mumford
Ioria, et al., J. Med. Chem. 34:2615-2623 (1991).
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-Aspartic Acid-Valine." J. Biol. Chem. 266:15075-15079 (1991).
Elices, Mariano "The Integrin .alpha..sub.r .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, Skaer A. et al., "Antiplatelet Efficacy and Specificity of DMP728, a Novel Platelet GP11B/IIIa Receptor Antagonist." Clin. Pharm. 83:373-382 (1993).
Pfaff, Martin et al., "Seletive 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).

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