For‐Met‐Lys‐Phe‐ For‐Met‐Lys‐Phe‐: A new cyclic analogue of the chemotactic formylpeptides

As a continuation of the studies on chemotactic N ‐formylpeptides, we report here the synthesis and activity of a new cyclic analogue of the prototypical ligand For‐Met‐Leu‐Phe‐OMe. The new compound contains a 20‐membered cyclic moiety made up of a dimeric‐Lys‐Phe‐sequence in which For‐Met is attached to each Lys α‐NH 2 ‐and hence remains outside the ring. The conformation in the crystal of the cyclic precursor of 4 , namely and the activity of the structurally related linear analogue For‐Met‐Lys(Z)‐Phe‐OBzl ( 6 ), have also been examined. The new analogues 4 and 6 are active as chemoattractants, secretagogues and superoxide anion generating agents, when tested on human neutrophils. The structure‐activity relationship is discussed and related to that of a previously studied cyclic model. © 1995 John Wiley & Sons, Inc.