Residue requirements for helical folding in short alpha/beta-peptides: crystallographic characterization of the 11-helix in an optimized sequence

J Am Chem Soc. 2005 Sep 28;127(38):13130-1. doi: 10.1021/ja0536163.

Abstract

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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Carbohydrate Sequence
  • Crystallography
  • Crystallography, X-Ray
  • Models, Molecular
  • Molecular Sequence Data
  • Peptides / chemistry*
  • Protein Folding*
  • Protein Structure, Secondary*

Substances

  • Peptides