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(z)Phe-OMe and HCO-Xaa-Leu-Delta( z)Phe-Phe-OMe structures (Delta(z)Phe = (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 corr esponding HCO-Xaa-Leu-Phe-OMe derivatives not containing the unsaturat ed residue. The replacement of the C-terminal Phe with Delta(z)Phe cau ses, in all the examined tripeptides, the loss of any biological activ ity. On the other hand, the introduction into the Delta(z)Phe containi ng models of an additional C-terminal Phe residue leads to the formylt etrapeptides HCO-Xaa-Leu-Delta(z)Phe-Phe-OMe which show a biological a ctivity very similar to that exhibited by the corresponding HCO-Xaa-Le u-Phe-OMe analogues.