Structure–activity relationship of for- l-Met l-Leu- l-Phe-OMe analogues in human neutrophils

Neutrophils migrate to infected tissues along a concentration gradient of chemoattractant molecules, e.g. for-Met-Leu-Phe-OMe (fMLP-OMe). The aim of the studies reported herein was twofold: to clarify the mechanisms whereby the ligand hooks its specific receptor and to verify the biological consequences arising from every possible variations on the fMLP-OMe prototype. Neutrophils constitute the first line of defence against bacterial invasion. They migrate to infected tissues along a concentration gradient of chemoattractant molecules, the most important of which is for-Met-Leu-Phe-OH (fMLP). Different responses arise from formylpeptides binding to different isoforms of the specific receptor. The aim of the studies reported herein was to clarify (i) the role of fMLP-OMe amide bonds in receptor–ligand cross-linking, (ii) the nature of the group occupying the N- and C-terminal positions, (iii) the features peculiar to the Met, Leu, and Phe receptor pockets, and (iv) the features which determine the specific neutrophil response.