The effect of the cyclopropyl group on the conformation of chemotactic formyl tripeptides

Abstract

Certain formyl peptides are powerful chemoattractants towards neutrophils. In this study, several formyl tripeptides were synthesized and used to investigate the effects of different amino acid residues in position 1 on their ability to stimulate neutrophil chemotaxis. Pig neutrophil chemotaxis towards the formyl tripeptide, HCO–Ac3C–Leu–Phe–OMe 1, where Ac3C represents 1-amino-1-cyclopropane carboxylic acid, was observed. Pig neutrophil chemotaxis towards a very similar formyl tripeptide, HCO–Aib–Leu–Phe–OMe 2, where Aib represents α-amino isobutyric acid, was not observed. Compared to the isopropyl group, it was shown that the cyclopropyl group induces a greater percentage of the E conformation about the formamide functionality in these peptides. For 1 and 2, the E isomer distributions in CDCl3 are 36 and 9%, respectively. Since a major difference between these two peptides is the Z/E isomeric distribution, one implication is that the peptide–receptor site interactions involving the E conformer are more effective than those of the Z conformer. No pig neutrophil chemotaxis towards the formyl tripeptides, HCO–Ala–Leu–Phe–OMe 3 and HCO–Gly–Leu–Phe–OMe 4 was observed. These formyl tripeptides exhibit a low percentage of the E isomer, similar to that of peptide 2.