MODIFIED CHEMOTACTIC PEPTIDES - SYNTHESIS, CRYSTAL CONFORMATION, AND ACTIVITY OF FOR-HSE(ME)-LEU-PHE-OME

The presence of the sulfur atom of the methionine side chain exerts si gnificant effects at different levels on biochemical behavior of chemo tactic N-formylpeptides. In order to acquire more information on this point, the synthesis, the conformation in the crystal, and the activit y of For-Hse(Me)-Leu-Phe-OMe (2)-an oxygen analogue of For-Met-Leu-Phe -OMe (fMLP-OMe) containing the O-methyl-L-homoserine in place of the n ative methionine at position 1-is reported. The new analogue 2 adopts a conformation that is extended at the first two residues and folded a t the C-terminal phenylalanine. This conformation is different from th at of the parent fMLP-OMe and strikingly similar to that adopted by fM LP-OBu(t). The side-chain spatial orientation of 2 corresponds to that adopted by fMLP-OH when cocrystallized with an immunoglobulin possess ing binding properties similar to those of neutrophil receptors. When tested on human neutrophils the formylpeptide 2 is more active than th e parent in the stimulation of directed mobility and maintains both th e granule enzyme release activity and the superoxide anion production. (C) 1994 John Wiley & Sons, Inc.