An unusual C-H ... O hydrogen bond mediated reversal of polypeptide chain direction in a synthetic peptide helix

Abstract

An unusual C-terminal conformation has been detected in a synthetic decapeptide designed to analyze the stereochemistry of helix termination in polypeptides. The crystal structure of the decapeptide Boc-Leu-Aib-Val-Ala-Leu-Aib-Val-^DAla-^DLeu-Aib-OMe reveals a helical segment spanning residues 1-7 and helix termination by formation of a Schellman motif, generated by ^DAla(8) adopting the left-handed helical (α_L) conformation. The extended conformation at ^DLeu(9) results in a compact folded structure, stabilized by a potentially strong C-H · · · O hydrogen bond between Ala(4) C^αH and ^DLeu(9) CO. The parameters for C-H · · · O interaction are Ala(4) C^αH · · O=C ^DLeu(9) distance 3.27 Å, C^α-H · · O angle 176°, and O · · H^α distance 2.29Å. This structure suggests that insertion of contiguous D-residues may provide a handle for the generation of designed structures containing more than one helical segment folded in a compact manner.