Cyclic CS-1 peptidomimetics, compositions and methods of using s

Details Cyclic CS-1 peptidomimetics, compositions and methods of using s Cyclic CS-1 peptidomimetics, compositions and methods of using s

1995-08-25

1999-02-09

Russel, Jeffrey E.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Peptide containing doai

530317, 530327, 530328, 530329, 530330, 530345, 930260, 930270, A61K 3808, A61K 3812, C07K 700, C07K 756

Patent

active

058694480

ABSTRACT:
The present invention contemplates a cyclic 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 cyclic peptide and processes for treating immunoinflammatory conditions using a binding-inhibitory cyclic peptide are also disclosed.

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patent: 5608035 (1997-03-01), Yanofsky et al.
Komoriya, Akira et al., "The Minimal Essential Sequence for a Major Cell Type-Specific Adhesion Site (CS1) Within the Alternatively Spliced Type III Connecting Segment Domain of Fibronectin is Leucine-Aspartic Acid-Valine." J. Biol. Chem. 266;15075-15079 (1991).
Wayner, E.A. et al., "Activation-dependent Recognition by Hematopoietic Cells of the LDV Sequence in the V Region of Fibronectin." J. Cell Biology 116 (2):489-497 (1990).
Cardarelli, Pina M et al., "Cylic RGD Peptide Inhibits .alpha.4.beta.1 Interaction with Connecting Segment 1 and Vascular Cell Adhesion Molecule." J. Biol. Chem. 269:18668-18673 (1994).
Hart, Stephen L. et al., "Cell Binding and Internalization by Filamentous Phage Displaying a Cyclic Arg-Gly-Asp-containing Peptide." J. Biol. Chem. 269:12468-12474 (1994).
Koivunen, Erkki et al., "Isolation of Highly Specific Ligand for the .alpha..sub.5 .beta..sub.1 Integrin from a Phage Display Library." J. Cell Biol. 124:373-380 (1994).
Mousa, Shaker A. et al., "Antiplatelet Efficacy and Specificity of DMP728, a Novel Platelet GPIIb/IIIa Receptor Antagonist." Cardiology 83:374-382 (1993).
Nowlin, Dawn M. et al., "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).
Pfaff, Martin et al., "Selective Recognition of Cyclic RGD Peptides of NMR Defined Conformation by .alpha.IIb.beta.3, and .alpha.5.beta.1 Integrins." J. Biol. Chem. 269:20233-20238 (1994).
Gurrath, Marion et al., "Conformation/Activity Studies of Rationally Designed Potent Anti-Adhesive RGD Peptides." Eur. J. Biochem. 210:911-921 (1992).
Kamber, Bruno et al., "The Synthesis of Cystine Peptides by Iodine Oxidation of S-Trityl-cysteine and S-Acetamidomethyl-cysteine Peptides." Helvetica Chimica Acta. 63:899-915 (1980).

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