Cyclic Peptides from Higher Plants. Part 32. Conformational Preference of Cycloleonuripeptides A, B, and C, Three Proline-Rich Cyclic Nonapeptides from Leonurus heterophyllus.

Abstract

Three-dimensional structures in dimethyl sulfoxide (DMSO)-d6 of three proline-rich cyclic nonapeptides, cycloleonuripeptides A : cyclo (-Gly-Pro-Pro-Pro-Tyr-Pro-Pro-Met-Ile-), B : cyclo (-Gly-Pro-Pro-Pro-Tyr-Pro-Pro-Met(O)-Ile-), and C : cyclo (-Gly-Pro-Pro-Pro-Tyr-Pro-Pro-Met(O)-Ile-), which have been isolated from the fruits of Leonurus heterophyllus, were determined by distance geometry calculation and restrained energy minimization from NMR data. Calculation using 272 different initial structures led to a uniquely determined backbone conformation with a root mean square deviation value of 0.57 A. The backbone structures of cycloleonuripeptides A, B, and C consist of two β-turns, a β VI turn at Pro3-Pro4, and a β I turn at Pro7-Met8. In addition to a transannular 4→1 backbone hydrogen bond between Tyr5-NH and Pro2-CO, two intramolecular hydrogen bonds between Gly1-NH and Pro6-CO, and between Ile9-NH and Pro6-CO, which constructed a β-bulge conformation, were observed.