Cycloleonuripeptide D, a new proline-rich cyclic decapeptide from Leonurus heterophyllus

Abstract

A new proline-rich cyclic decapeptide, cycloleonuripeptide D (1), cyclo (-Ser-Pro-Pro-Tyr-Phe-Gln-Thr-Pro-Ile-), was isolated from the fruits of Leonurus heterophyllus and the structure was elucidated by extensive 2D NMR, chemical and enzymatic degradation studies, and tandem MS method. The solid state conformation of cycloleonuripeptide D was clarified by X-ray diffraction study. The cyclic decapeptide backbone of 1 contained two β-turns, one type I β-turn at Pro-Ile and one type III β-turn at Pro-Tyr. A transannular 4 → 1 backbone hydrogen bond between Ser-NH and Thr-CO, and a 5 → 1 hydrogen bond between Phe-NH and Pro-Co encompassing Pro-Pro-Tyr, in which the peptide linkage between the two proline residues was shown to be in the cis conformation, were observed.