Effects of Cα‐methyl substitution on the conformation of linear GnRH antagonist analogs

Publisher Website
Google Scholar
Abstract
We have examined the effect of Cα‐methyl groups on the conformational ensemble of GnRH analog peptides by comparing 1H 2D NMR data from two analogs, Ac‐D‐Nal1‐D‐4‐Cl‐Cα‐Me‐Phe2‐D‐Pal3‐Ser4‐Tyr5‐D‐Arg6‐Leu7‐Arg8‐Pro9‐D‐Ala10‐NH2(1)andAc‐D‐Nal1‐D‐4‐CI‐Cα‐Me‐Phe2‐D‐Pal3‐Ser4‐Cα‐Me‐Tyr5‐D‐Arg6‐Leu7‐Cα‐Me‐Arg8‐Pro9‐D‐Ala10‐NH2 (2). The two additional Cα‐methyl groups in residues 5 and 8 of 2 do not influence significantly the pattern of the observable main chain NOE intensities, or of the backbone HN proton chemical shifts, which indicates that 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‐Arg8‐Pro9.