Nature of amide carbonyl--carbonyl interactions in proteins

J Am Chem Soc. 2009 Jun 3;131(21):7244-6. doi: 10.1021/ja901188y.

Abstract

Noncovalent interactions define and modulate biomolecular structure, function, and dynamics. In many protein secondary structures, an intimate interaction exists between adjacent carbonyl groups of the main-chain amide bonds. As this short contact contributes to the energetics of protein conformational stability as well as protein-ligand interactions, understanding its nature is crucial. The intimacy of the carbonyl groups could arise from a charge-charge or dipole-dipole interaction, or n-->pi * electronic delocalization. This last putative origin, which is reminiscent of the Burgi-Dunitz trajectory, involves delocalization of the lone pairs (n) of the oxygen (O(i-1)) of a peptide bond over the antibonding orbital (pi*) of the carbonyl group (C(i)=O(i)) of the subsequent peptide bond. By installing isosteric chemical substituents in a peptidic model system and using NMR spectroscopy, X-ray diffraction analysis, and ab initio calculations to analyze the consequences, the intimate interaction between adjacent carbonyl groups is shown to arise primarily from n-->pi* electronic delocalization. This finding has implications for organic, biological, and medicinal chemistry.

MeSH terms

  • Amides / chemistry*
  • Electrons*
  • Protein Conformation
  • Proteins / chemistry*
  • Static Electricity

Substances

  • Amides
  • Proteins