SYNTHESIS, CONFORMATION, AND BIOLOGICAL-ACTIVITY OF 2 FMLP-OME ANALOGS CONTAINING THE NEW 2-[2'-(METHYLTHIO)ETHYL] METHIONINE RESIDUE

The new C-alpha-tetrasubstituted alpha-amino acid residue 2-[2'(methyl thio)ethyl]methionine (Dmt) has been introduced into the reference che motactic tripeptide HCO-Met-Leu-Phe-Ome (fMLP-OMe) in place of the leu cine or methionine, respectively. The biological activity of the new a nalogues [Dmt(2)]fMLP-OMe (2) and [Dmt(1)]fMLP-OMe (3) has been determ ined; whereas 2 is active toward human neutrophils, stimulating direct ed migration, superoxide anion generation, and lysozyme release, 3 res ults practically inactive in all tested assays. A conformational analy sis on 2 and 3 has been performed in solution by using ir absorption a nd H-1-nmr. The conformation of 2 was also examined in the crystal by x-ray diffraction methods. Both 2 and 3 adopt fully extended conformat ion in correspondence with the Dmt residue. Biological and conformatio nal results are discussed and compared with related previously studied models. (C) 1997 John Wiley & Sons, Inc.