Signature of n ->pi* interactions in alpha-helices

The oxygen of a peptide bond has two lone pairs of electrons. One of these lone pairs is poised to interact with the electron-deficient carbon of the subsequent peptide bond in the chain. Any partial covalency that results from this n ->pi* interaction should induce pyramidalization of the carbon (C'(i)) toward the oxygen (Oi-1). We searched for such pyramidalization in 14 peptides that contain both alpha-and beta-amino acid residues and that assume a helical structure. We found that the alpha-amino acid residues, which adopt the main chain dihedral angles of an alpha-helix, display dramatic pyramidalization but the beta-amino acid residues do not. Thus, we conclude that Oi-1 and C'(i) are linked by a partial covalent bond in alpha-helices. This finding has important ramifications for the folding and conformational stability of alpha-helices in isolation and in proteins.