Peptide inhibitors of inflammation

Details Peptide inhibitors of inflammation Peptide inhibitors of inflammation

C - Chemistry, Metallurgy

07

K

C07K 7/08 (2006.01) A61K 38/08 (2006.01) A61K 38/10 (2006.01) C07K 7/06 (2006.01) C07K 14/705 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2103139

2103139 9220708 PCTABS00017 Peptides derived from three regions of the lectin domain of GMP-140 and the related selectins, ELAM-1 and the lymphocyte homing receptor, have been found to inhibit neutrophil adhesion to GMP-140. These and additional peptides have been synthesized, having as their core region portions of the 23-30 amino acid sequence of GMP-140, with residue 1 defined as the N-terminus of the mature protein after the cleavage of the signal peptide. Examples demonstrate the inhibition of the binding of neutrophils to GMP-140 of peptides in concentrations ranging from 5 to 1500 µM. It has been found that alterations within the core sequence, as well as N-terminal and C-terminal flanking regions, do not result in loss of biological activity. It has also been found that certain of these modifications can significantly increase the stability of peptides of Formula (I) or (II) against degradation by the enzymes found in human serum. The peptides are useful as diagnostics and, in combination with a suitable pharmaceutical carrier, for clinical applications in the modulation or inhibition of coagulation processes or inflammatory processes.

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