Hitesh Shroff

Sulfonopeptide inhibitors of leukocyte adhesion

Abstract The amino acid sequence L-D-T-S-L has been shown to be a significant recognition motif involved in the interaction of integrin α4β7 with its endothelial ligand, MAdCAM-1. Based on the known active peptide, a series of sulfonamide peptidomimetics was synthesized. Sulfonopeptide 2, Ac-L-ψD-V-NH2, was shown to inhibit leukocyte adhesion.

Small peptide inhibitors of α4β7 mediated MAdCAM-1 adhesion to lymphocytes

Specificity of leukocyte trafficking to intestinal mucosal tissues is largely mediated by MAdCAM-1α4β7 interaction. A series of small peptides was prepared to establish L-D-T-S-L as a recognition motif involved in the α4β7 interaction. N-Terminus acylation of the L-D-T-S-L motif has led to low micromolar inhibitors of leukocyte adhesion. Leukocyte trafficking to intestinal mucosal tissues is largely mediated by a MAdCAM-1α4β7 interaction. A series of small peptides were prepared to establish L-D-T-S-L as a recognition motif involved. N-Terminus acylation of the L-D-T-S-L yielded micromolar inhibitors of leukocyte adhesion.

Novel modified tripeptide inhibitors of α4β7 mediated lymphoid cell adhesion to MAdCAM-1

MAdCAM-1 specifically binds the lymphocyte integrin α4β7 and participates in the homing of leukocytes to intestinal mucosal sites. The LDT sequence located on the CD loop of MAdCAM-1 is an important binding site for MAdCAM-1/α4β7 interactions. N-Terminus acylation of the LDT motif and modification of the C-terminus carboxamide with amines led to low micromolar MAdCAM-1 inhibitors.