CONFORMATIONAL PREFERENCE OF CYCLOLEONURIPEPTIDE-A, CYCLOLEONURIPEPTIDE-B, AND CYCLOLEONURIPEPTIDE-C, 3 PROLINE-RICH CYCLIC NONAPEPTIDES FROM LEONURUS-HETEROPHYLLUS

Three-dimensional structures in dimethyl sulfoxide (DMSO)-d(6) of thre e proline-rich cyclic nonapeptides, cycloleonuripeptides A: cycle (-Gl y-Pro-Pro-Pro-Tyr-Pro-Pro-Met-Ile), B: cycle (-Gly-Pro-Pro-Pro-Tyr-Pro -Pro-Met(O)-Ile-), and C: cycle (-Gly-Pro-Pro-Pro-Tyr-Pro-Pro-Met(O)-I le-) which have been isolated from the fruits of Leonurus heterophyllu s, were determined by distance geometry calculation and restrained ene rgy minimization from NMR data. Calculation using 272 different initia l structures led to a uniquely determined backbone conformation with a root mean square deviation value of 0.57 Angstrom. The backbone struc tures of cycloleonuripeptides A, B, and C consist of two beta-turns, a beta VI turn at Pro(3)-Pro(4), and a beta I turn at Pro(7)-Met(8). In addition to a transannular 4-->1 backbone hydrogen bond between Tyr(5 )-NH and Pro(2)-CO, two intramolecular hydrogen bonds between Gly(1)-N H and Pro(6)-CO, and between ILe(9)-NH and Pro(6)-CO, which constructe d a beta-bulge conformation, were observed.