Homooligomeric β3 (R)-valine peptides: Transformation between C14 and C12 helical structures induced by a guest Aib residue.

Abstract

Novel helical, structures unprecedented in the chemistry of α-polypeptides, may be found in polypeptides containing β and γ amino acids. The structural characterization of C12 and C14 -helices in oligo β-peptides was originally achieved using conformationally constrained cyclic β-residues. This study explores the conformational characteristics of proteinogenic β3 residues in homooligomeric sequences and addresses the issue of inducing a transition between C14 and C12 helices by the introduction of a guest α-residue. Folded C14 -helical structures are demonstrated for the nonapeptide Boc-[β3 (R)Val]9 -OMe by NMR methods in CDCl3 -DMSO mixtures, while the peptide was found to be aggregated in CDCl3 . The insertion of a guest Aib residue into an oligo-β-valine sequence in the octapeptide model Boc-[(β3 (R)Val)3 -Aib-(β3 (R)Val]4 -OMe results in well dispersed NH region in the NMR spectrum indicating folded structures in CDCl3 . Structure calculations for both the peptides using NOE distance constraints support a C14 helical structure in the homooligomer which transform into a C12 helix on introduction of the guest Aib residue.