CHEMOTACTIC PEPTIDE ANALOGS - CENTRALLY CONSTRAINED CHEMOTACTIC N-FORMYLTRIPEPTIDES - SYNTHESIS, CONFORMATION, AND ACTIVITY OF 2 NEW ANALOGS

The role exercised by the central residue of the chemotactic N-for-myl tripeptide HCO-Met-Leu-Phe-OMe (fMLP-OMe) in controling both the backb one conformation and the biochemical activity is the subject of recent interest. Hen, two new centrally constrained fMLP-OMe analogues, name ly HCO-Met-aza-Pro-Phe-OMe (4) and HCO-Met-(gamma-lactam)-Phe-OMe (6) have been synthesized and their CDCl3 solution conformation and activi ty have been studied. The azapeptide 3 adopts beta-folded conformation with the azaPro residue at the i+2 position and an intramolecular H-b ond involving the formylic oxygen and the Phe NH. The gamma-lactam tri peptide 6 prefers a semi-extended backbone conformation. When tested o n human neutrophils both the new models were found practically devoid of biological activity. The role exerted by the NH groups as well as b y the conformational preferences is discussed.