Conformationally constrained chemotactic peptide analogs of high biological activity

Abstract

The stereochemically constrained chemotactic peptide analogs,formylmethionyl-α-aminoisobutyrylphenylalanine (formyl-Met-Aib-Phe-OH) and formylmethionylcycloleucinylphenylalanine (formyl-Met-Cyl-Phe-OH) are highly effective in inducing lysosomal enzyme release from rabbit neutrophils. NMR studies of the Aib² analog in (CD₃)₂SO favor a folded conformation in which the Phe NH group is inaccessible to solvent. Intramolecularly hydrogen-bonded conformations involving a Met-Aib-β-turn or a γ-turn centered at Aib² are considered. The results suggest that folded conformations may allow highly active interactions with the neutrophil formylpeptide receptor.