A highly stable short alpha-helix constrained by a main-chain hydrogen-bond surrogate

J Am Chem Soc. 2004 Oct 6;126(39):12252-3. doi: 10.1021/ja0466659.

Abstract

Herein we describe a strategy for the preparation of artificial alpha-helices involving replacement of one of the main-chain hydrogen bonds with a covalent linkage. To mimic the C=O...H-N hydrogen bond as closely as possible, we envisioned a covalent bond of the type C=X-Y-N, where X and Y are two carbon atoms connected through an olefin metathesis reaction. Our results demonstrate that the replacement of a hydrogen bond between the i and i + 4 residues at the N-terminus of a short peptide with a carbon-carbon bond results in a highly stable constrained alpha-helix at physiological conditions as indicated by CD and NMR spectroscopies. The advantage of this strategy is that it allows access to short alpha-helices with strict preservation of molecular recognition surfaces required for biomolecular interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / chemistry*
  • Circular Dichroism
  • Glutamic Acid / chemistry*
  • Hydrogen Bonding
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptides / chemistry*
  • Protein Structure, Secondary

Substances

  • Peptides
  • Glutamic Acid
  • Alanine