Texas Biotechnology Corporation

Pamela J Beck

Timothy P Kogan

Peter Vanderslice

Kaijun Ren

Brian Dupre

Huong Dao

Ian Leslie Scott

Karin M Keller

The present invention is directed to an isolated and purified cyclic peptide of from 5 to about 13 residues modeled after a portion of the CS1 peptide. A peptide of this invention preferably has the amino acid residue sequence of SEQ ID NO:2-14 or 16-42. The present invention is further directed to a process of selectively inhibiting the binding of &agr; &bgr; integrin to a protein such as VCAM-1, fibronectin or invasin. In accordance with that process, a cell that expresses &agr; &bgr; integrin is exposed to that protein in the presence of an effective inhibiting amount of such a peptide. The present invention is still further directed to a pharmaceutical composition containing a physiologically acceptable carrier and a cyclic peptide of the invention.

Process to inhibit binding of the integrin &agr;4&bgr;1 , to VCAM-1 fibronectin and cyclic peptides thereof

The present invention is directed to an isolated and purified cyclic peptide of from 5 to about 13 residues modeled after a portion of the CS1 peptide. A peptide of this invention preferably has the amino acid residue sequence of SEQ ID NO:2-14 or 16-42. The present invention is further directed to a process of selectively inhibiting the binding of .alpha..sub.4 .beta..sub.1 integrin to a protein such as VCAM-1, fibronectin or invasin. In accordance with that process, a cell that expresses .alpha..sub.4 .beta..sub.1 integrin is exposed to that protein in the presence of an effective inhibiting amount of such a peptide. The present invention is still further directed to a pharmaceutical composition containing a physiologically acceptable carrier and a cyclic peptide of the invention.

Process to inhibit binding of the integrin .alpha..sub.4 .beta..sub.1 to

This invention relates to compounds that inhibit the binding of E-selectin or P-selectin to sialyl-Lewis.sup.x or sialyl-Lewis.sup.a presented on a cell surface having the general structure: ##STR1## This invention also relates to methods of inhibiting the binding of E-selectin or P-selectin to sialyl-Lewis.sup.x or sialyl-Lewis.sup.a presented on a cell surface using said compounds and to pharmaceutically active compositions comprising compounds that inhibit the binding of E-selectin to sialyl-Lewis.sup.x and to methods of treatment of septic shock, ARDS, Crohn's disease, chronic inflammatory diseases, such as psoriasis and rheumatoid arthritis, and reperfusion injuries that occurs following heart attacks, strokes and organ transplants and to the treatment of cancer.

Compositions and methods of inhibiting the binding of E-selectin or

The present invention is directed to an isolated and purified peptide comprising the LDV domain of the CSI peptide sequence or single amino acid substitutent analog thereof. A preferred peptide has the amino acid residue sequences shown in SEQ ID NOs:8-14, 17-23, 25, 28, and 51. The present invention is further directed to a process of inhibiting the binding of .alpha..sub.4 .beta..sub.1 integrin to a protein such as VCAM-1 or fibronectin comprising exposing a cell that expresses .alpha..sub.4 .beta..sub.1 integrin to the protein in the presence of an effective inhibiting amount of such a peptide. The present invention is still further directed to a pharmaceutical composition comprising a peptide of SEQ ID NO:8-102.

Process to inhibit binding of the integrin .alpha..sub.4 62 .sub.1 to

This invention relates to compounds that inhibit the binding of E-selectin and/or P-selectin to sialyl-Lewis.sup.x or sialyl-Lewis.sup.a presented on a cell surface having the general structure ##STR1## wherein X is selected from the group consisting of --(CH.sub.2).sub.n CO.sub.2 H, --O(CH.sub.2).sub.m CO.sub.2 H, --(CH.sub.2).sub.n O(CH.sub.2).sub.m CO.sub.2 H, --CONH(CH.sub.2).sub.m CO.sub.2 H, --CH(OZ)(CO.sub.2 H), --CH(Z)(CO.sub.2 H), --(CH.sub.2).sub.n SO.sub.3 H, --(CH.sub.2).sub.n PO.sub.3 D.sub.1 D.sub.2, --NH(CH.sub.2).sub.m CO.sub.2 H, --CONH(CHR.sub.6)CO.sub.2 H, (1-H-tetrazolyl-5-alkyl-), and --OH;

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Houston, TX, United States of America

Pamela J Beck