Influence of α-methylation in constructing stapled peptides with olefin metathesis

Ring-closing metathesis is commonly utilized in peptide macro-cyclization. The influence of alpha-methylation of the amino acids bearing the olefin moieties has never been systematically studied. In this report, controlled reactions unambiguously indicate that alpha-methylation at the N-terminus of the metathesis sites is crucial for this reaction to occur. Also, we first elucidated that the E-isomers of stapled peptides are significantly more helical than the Z-isomers. (C) 2014 Elsevier Ltd. All rights reserved.