Synthesis and activity on human neutrophil functions of fMLF-OMe analogs containing alkyl spacers at the central position

Abstract

We report here the synthesis and activity of new analogs of the N-formyl and N- tert-butyloxycarbonyl (Boc) derivatives of the tripeptide Met-Leu-Phe-OMe containing an achiral ω-amino acid residue replacing the hydrophobic central leucine. The tripeptides HCO-Met-NH-(CH 2) n -CO-Phe-OMe and Boc-Met-NH-(CH 2) n -CO-Phe-OMe ( n=3–5) containing the central homomorphic residue of 5-aminopentanoic acid (δ-aminovaleric acid; δ-Ava; n=4) and the two non-homomorphic residues of 4-aminobutanoic acid (γ-aminobutyric acid; γ-Abu; n=3) and 6-aminohexanoic acid (ε-aminocaproic acid; ε-Aca; n=5) have been examined. The activity as agonists and antagonists in chemotaxis, lysozyme release, and superoxide anion production of the new analogs has been determined. The N-Boc derivatives 2a and 2b, incorporating the γ-Abu and the δ-Ava residues, show good and selective antagonist activity on superoxide anion production.