Bioactive fMLF-OMe analogs containing a N-terminal oximic or formylhydrazonic moiety

In order to obtain chemotactic peptides with selective bioactivity, a new type of structural modification was introduced at the N-terminal position of HCO-Nle-Leu-Phe-OMe. Two groups of analogs have been synthesized both containing a N-terminal residue of the X=C(R)-CO-type replacing the native HCO-NH-CH(R)-CO-. In particular, the A group of pseudopeptides (2a-d) possesses a N-terminal oximic fragment (X=HO-N) and the B group (3a-d) a formylhydrazone fragment (X=HCO-NH-N). These new ligands have been examined for their capacity to induce chemotaxis and other cellular responses such as superoxide anion production and lysozyme release; although significantly active as chemoattractants they have been found to be practically devoid of secretagog activity, thus exhibiting selective behavior. The adopted chemical modification seems extensible in designing a new class of pseudopeptides (hydrazonopeptides) structurally related to both hydrazinopeptides and peptides containing alpha,beta-unsaturated residues.