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 significant effects at different levels on biochemical behavior of chemotactic N ‐formylpeptides. In order to acquire more information on this point, the synthesis, the conformation in the crystal, and the activity of For‐Hse(Me)‐Leu‐Phe‐OMe (2) —an oxygen analogue of For‐Met‐Leu‐Phe‐OMe (f MLP‐OMe) containing the O ‐methyl‐ L ‐homoserine in place of the native methionine at position 1—is reported. The new analogue 2 adopts a conformation that is extended at the first two residues and folded at the C ‐terminal phenylalanine. This conformation is different from that of the parent f MLP‐OMe and strikingly similar to that adopted by f MLP‐OBu t . The side‐chain spatial orientation of 2 corresponds to that adopted by f MLP‐OH when cocrystallized with an immunoglobulin possessing binding properties similar to those of neutrophil receptors. When tested on human neutrophils the formylpeptide 2 is more active than the parent in the stimulation of directed mobility and maintains both the granule enzyme release activity an the superoxide anion production. © 1994 John Wiley & Sons, Inc.