Synthesis, and Helix or Hairpin‐Turn Secondary Structures of ‘Mixed’ α/β‐Peptides Consisting of Residues with Proteinogenic Side Chains and of 2‐Amino‐2‐methylpropanoic Acid (Aib)

Abstract

Twelve peptides, 1–12, have been synthesized, which consist of alternating sequences of α‐ and β‐amino acid residues carrying either proteinogenic side chains or geminal dimethyl groups (Aib). Two peptides, 13 and 14, containing 2‐methyl‐3‐aminobutanoic acid residues or a ‘random mix’ of α‐, β2‐, and β3‐amino acid moieties were also prepared. The new compounds were fully characterized by CD (Figs. 1 and 2), and 1H‐ and 13C‐NMR spectroscopy, and high‐resolution mass spectrometry (HR‐MS). In two cases, 3 and 14, we discovered novel types of turn structures with nine‐ and ten‐membered H‐bonded rings forming the actual turns. In two other cases, 8 and 11, we found 14/15‐helices, which had been previously disclosed in mixed α/β‐peptides containing unusual β‐amino acids with non‐proteinogenic side chains. The helices are formed by peptides containing the amino acid moiety Aib in every other position, and their backbones are primarily not held together by H‐bonds, but by the intrinsic conformations of the containing amino acid building blocks. The structures offer new possibilities of mimicking peptide–protein and protein–protein interactions (PPI). © 2006 Verlag Helvetica Chimica Acta