Synthesis, and helix or hairpin-turn secondary structures of 'mixed' alpha/beta-peptides consisting of residues with proteinogenic side chains and of 2-amino-2-methylpropanoic acid (Aib)

Twelve peptides, 1-12, have been synthesized, which consist of alternating sequences of alpha- and beta-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 alpha-, beta(2)-, and beta(2)-amino acid moieties were also prepared. The new compounds were fully characterized by CD (Figs. 1 and 2), and H-1- and C-13-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 alpha/beta-peptides containing unusual beta-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).