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

1995-06-05

1998-06-23

Tsang, Cecilia J.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Peptide containing doai

514 19, 514386, 514392, 530331, 5483164, A61K 3805, A61K 3806, C07K 504

Patent

active

057705739

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.

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Mould et al., "The CS5 Peptide Is a Second Site in the IIICS Region of Fibronectin Recognized by the Integrin .alpha..sub.4 .alpha..sub.1 " J. of Biol. Chem., vol. 266, No. 6, pp. 3579-3585, Feb. 25, 1991.
Esser, F. and Roos, O. "N-Terminal Cyclization of Peptides with N,N'-Carbonyldimidazole or N,N'-Thiocarbonylidiimidazole." Angew. Chem. Int. Ed. Engl. 17(6):467-468 (1978).
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.4 .beta..sub.1 (VLA-4) as a Therapeutic Target." Cell Adhesion and Human Disease. Wiley, Chicester (Ciba Foundation Symposium 1989) pp. 79-90 (1995).
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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).

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