Critical Main-Chain Length for Conformational Conversion From 3(10)-Helix to α-Helix in Polypeptides.

Abstract To assess the minimal peptide length required for the stabilization of the a-helix relative to the 3(10)-helix in Aib-rich peptides, we have solved the X-ray diffraction structures of the terminally blocked sequential hexa- and octapeptides with the general formula -(Aib-L-Ala)(n)-(n = 3 and 4, respectively). The hexapeptide molecules are completely 3(10)-helical with four 1 ← 4 intramolecular N-H … O=C H-bonds. On the other hand, the octapeptide molecules are essentially α-helical with four 1 ← 5 H-bonds; however, the helix is elongated at the N-terminus, with two 1 ← 4 H-bonds, giving these molecules a mixed α/3(10)-helical character. In both compounds the right-handed screw sense of the helix is dictated by the presence of the Ala residues of L-configuration. This study represents the first experimental proof for a 3(10) →α-helix conversion in the crystal state induced by peptide backbone lengthening only.