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.
Torrini
I
I
Dipartimento di Studi Farmaceutici and Centro di Studio per la Chimica del Farmaco del CNR, Università La Sapienza, Roma, Italy.
Paglialunga Paradisi
M
M
Pagani Zecchini
G
G
Lucente
G
G
Mastropietro
G
G
Spisani
S
S
D002630:Chemotactic Factors / Q000494:pharmacology*; D006801:Humans; D006835:Hydrazones / Q000737:chemistry*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives*; D009504:Neutrophils / Q000187:drug effects*; D010091:Oximes / Q000737:chemistry*
D002630:Chemotactic Factors; D006835:Hydrazones; D010091:Oximes; D009240:N-Formylmethionine Leucyl-Phenylalanine