EFFECTS OF C-ALPHA-METHYL SUBSTITUTION ON THE CONFORMATION OF LINEAR GNRH ANTAGONIST ANALOGS

We have examined the effect of C-alpha-methyl groups on the conformati onal ensemble of GnRH analog peptides by comparing H-1 2D NMR data fro m two analogs, Tyr(5)-D-Arg(6)-Leu(7)-Arg(8)-Pro(9)-D-Ala(10)-NH2 (1) and r(6)-Leu(7)-C-alpha-Me-Arg(8)-Pro(9)-D-Ala(10)-NH2 (2). The two ad ditional C-alpha-methyl groups in residues 5 and 8 of 2 do not influen ce significantly the pattern of the observable main chain NOE intensit ies, or of the backbone HN proton chemical shifts, which indicates tha t they do not produce global changes in the conformational ensemble of the peptide. A local change induced by the substitution was observed in the conformation at D-Arg(8)-Pro(9). (C) Munksgaard 1994.