Heterocyclic peptide backbone modifications in an alpha-helical coiled coil

J Am Chem Soc. 2004 Dec 1;126(47):15366-7. doi: 10.1021/ja0450408.

Abstract

In this paper, we present 1,2,3-triazole epsilon2-amino acids incorporated as a dipeptide surrogate at three positions in the sequence of a known alpha-helical coiled coil. Biophysical characterization indicates that the modified peptides retain much of the helical structure of the parent sequence, and that the thermodynamic stability of the coiled coil depends on the position of the incorporation of the epsilon-residue. Crystal structures obtained for each peptide give insight into the chemical behavior and conformational preferences of the non-natural amino acid and show that the triazole ring can participate in the backbone hydrogen bonding of the alpha-helix as well as template an interhelical crossing between chains in the bundle.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Amino Acids / chemistry
  • Crystallography, X-Ray
  • DNA-Binding Proteins / chemistry*
  • Dipeptides / chemistry
  • Hydrogen Bonding
  • Leucine / analogs & derivatives*
  • Leucine / chemistry
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Kinases / chemistry*
  • Protein Structure, Secondary
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Thiazoles / chemistry*

Substances

  • Amino Acids
  • DNA-Binding Proteins
  • Dipeptides
  • Saccharomyces cerevisiae Proteins
  • Thiazoles
  • Protein Kinases
  • Leucine