Structure-function studies on synthetic peptides derived from the 109-118 lectin domain of selectins

Previously, we identified several peptides corresponding to amino acid sequences within the lectin domains of selectins that inhibit neutrophil (PMN) adhesion to P-selectin. Here we focused on one of the active regions, 109-118, which contains residues that have been identified as critical for E-selectin binding to the sialyl Lexis X (sLex) counter receptor. Analogues were synthesized and examined for their inhibitory effect on PMN binding to P-selectin and E-selectin immunoglobulin fusion proteins (P-IgG, E-IgG) and also on P-IgG and E-IgG binding to sLex coated surfaces. Peptide sequences which inhibited PMN binding to the fusion proteins were not necessarily those that inhibited fusion protein binding to sLex. In addition, various amino acid substitutions could be tolerated at the 111 and 113 positions without altering inhibitory activity. Modeling suggests that structural conformations of peptide analogues could explain the differences in biological activity of peptide analogues compared to mutants of the native protein.