FOR-MET-LYS-PHE-FOR-MET-LYS-PHE- - A NEW CYCLIC ANALOG OF THE CHEMOTACTIC FORMYLPEPTIDES

As a continuation of the studies of chemotactic N-formylpeptides, we r eport here the synthesis and activity of a new cyclic analogue of the prototypical ligand For-Met-Leu-Phe-OMe. The new compound For-Met-Lys- Phe-For-Met-Lys-Phe- (4) contains a 20-membered cyclic moiety made up of a dimeric -Lys-Phe- sequence in which For-Met is attached to each L ys alpha-NH2 and hence remains outside the ring. The conformation in t he crystal of the cyclic precursor of 4, namely Boc-Lys-Phe-Boc-Lys-Ph e- (2) and the activity of the structurally related linear analogue Fo r-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 structu re-activity relationship is discussed and related to that of a previou sly studied cyclic mode. (C) 1995 John Wiley & Sons, Inc.