Synthesis, biological activity, conformational analysis by NMR and molecular modeling of <i>N</i>‐formyl‐L‐Met‐L‐Pro‐L‐Phe‐OMe, a praline analogue of the chemotactic peptide <i>N</i>‐formyl‐L‐Met‐L‐Leu‐L‐Phe‐OH

Abstract

The tripeptide N-formyl-Met-Pro-Phe-OMe (f-MPF-OMe), an analogue of the signal peptide N-formyl-Met-Leu-Phe-OH (f-MLF-OH), was synthesized and its chemotactic activity evaluated; it showed no activity in either superoxide production or calcium mobility with human neutrophils. However, the corresponding acid f-MPF-OH retained about 25% activity in the production of superoxide. The conformation of the f-MPF-OMe analogue was evaluated by NMR spectroscopy and molecular simulation and shown to predominate in a gamma-turn with a hydrogen bond between Met CO and Phe NH. Since this analogue is not chemotactic, it is suggested that for recognition the receptor prefers a peptide with a flexible backbone, favoring an extended conformation in the binding site.