Formyl peptide chemoattractants: a model of the receptor on rabbit neutrophils

Twenty small molecular weight peptides related to the chemotactic peptide N-formylmethionylleucyl-phenylalanine (CHO-Met-Leu-Phe-OH) have been prepared by classical peptide synthesis. Compounds were prepared to evaluate the requirements in position 2 (leucine) and the C-terminal carboxyl group. Each analogue was tested for its ability to induce lysosomal enzyme release from cytochalasin B treated rabbit polymorphonuclear leukocytes. In addition, representative samples were also tested for their ability to inhibit specific binding of a super(3)H-labeled chemotactic peptide (CHO-Nle-Leu-( super(3)H)Phe-OH). The results indicate that both linear aliphatic and branched aliphatic residues in position 2 result in potent chemoattractants. Analysis of these data as well as previously published data for position 1 (methionine) indicates that hydrophobicity is a major determinant of biological activity. So that the role of the C-terminal area of the molecule could be probed, a number of tripeptide benzyl esters and the benzylamide derivative of CHO-Met-Leu-Phe-OH were prepared. These were uniformly more active than their free acid counterparts. These data as well as previously published data have been analyzed, and a hypothetical model of the chemotactic peptide receptor of rabbit neutrophil is presented.