Effects of C^α‐methyl substitution on the conformation of linear GnRH antagonist analogs

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.

Acridine−N Peptide Conjugates Display Enhanced Affinity and Specificity for boxB RNA Targets

“…Stabilizing the helical form of such peptides is expected to favor RNA binding by virtue of preorganization. For example, C R -substituted amino acids have long been recognized as a means of introducing local conformational restriction into peptides (48). Another approach to stabilize the R-helical form of peptides is through the incorporation of covalent linkages between constituent amino acid side chains.…”