A New Strategy to Induce γ-Turns: Peptides Composed of Alternating α-Aminoxy Acids and α-Amino Acids

Abstract

It is known that the seven-membered-ring intramolecular hydrogen bond (γ-turn) is seldom formed in naturally occurring peptides composed of α-amino acids. Here we report a new strategy to induce γ-turns in short linear peptides. We designed and synthesized several peptides (1-5) containing alternating α-L-aminoxy acids and α-D-amino acids. 1H NMR studies revealed that the γ-turn could be initiated by the following N-O turn, an eight-membered-ring intramolecular hydrogen bond induced by an α-aminoxy acid. Moreover, NOESY and CD studies suggested peptides 4 and 5 form a novel secondary structure, a mixed 7-8 helix. Theoretical calculations on several di-, tri-, and tetrapeptide models provided strong support to the above conclusions. Copyright © 2003 American Chemical Society.