Residue Requirements for Helical Folding in Short α/β-Peptides: Crystallographic Characterization of the 11-Helix in an Optimized Sequence

Abstract

Design of functional foldamers requires knowledge of the conformational propensities of constituent residues. Here, we explore the effects of variations in both α-amino acid and β-amino acid substitution on α/β-peptide helicity. We also report the first X-ray crystal structure of a helical α/β-peptide. We conclude that a certain amount of conformational preorganization in α/β-peptides (via the inclusion of constrained β-amino acids or α,α-disubstituted α-amino acids) is needed to promote helical folding; acyclic β-amino acids and β-branched α-amino acids are tolerated to only a limited extent.