Alpha Helix Nucleation by a Simple Cyclic Tetrapeptide

Abstract

The simple cyclic tetrapeptide cyclo-(1,4)-[Ala-Arg-Ala-homoGlu]-NH2 (3) is shown to adopt an unusual α-turn structure, which is not α-helical but can nucleate α-helicity when attached to the N-terminus of either model peptides or two biologically relevant peptides. This new N-terminal helix-capping macrocycle provides very simple and rapid synthetic access to α-helical peptide structures.