The role of (Z)-2,3-didehydrophenylalanine and phenylalanine C-terminal residues in determining the chemotactic activity of formylpeptides.
Several formylpeptides, analogs of the chemotactic agent HCO-Met-Leu-Phe-OMe, having the HCO-Xaa-Leu-delta ZPhe-OMe and HCO-Xaa-Leu-delta ZPhe-Phe-OMe structures (delta ZPhe = (Z)-2,3-didehydrophenylalanine), have been synthesized. The biological activity of these ligands has been determined on human neutrophils and compared to that of the corresponding HCO-Xaa-Leu-Phe-OMe derivatives not containing the unsaturated residue. The replacement of the C-terminal Phe with delta ZPhe causes, in all the examined tripeptides, the loss of any biological activity. On the other hand, the introduction into the delta ZPhe containing models of an additional C-terminal Phe residue leads to the formyltetrapeptides HCO-Xaa-Leu-delta ZPhe-Phe-OMe which show a biological activity very similar to that exhibited by the corresponding HCO-Xaa-Leu-Phe-OMe analogues.
Torrini
I
I
Dipartimento di Studi Farmaceutic, Università La Sapienza, Roma, Italy.
Zecchini
G P
GP
Paradisi
M P
MP
Spisani
S
S
D000595:Amino Acid Sequence; D002630:Chemotactic Factors / Q000138:chemical synthesis* / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D005561:Formates / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects*; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D002630:Chemotactic Factors; D005561:Formates; D009842:Oligopeptides; D010649:Phenylalanine; C018632:phenyldehydroalanine