SOLUTION-STATE CONFORMATION OF AN IMMUNOSUPPRESSIVE CYCLIC DODECAPEPTIDE, CYCLOLEONURININ

The cyclic dodecapeptide, cycloleonurinin, lo(-Gly-Pro-Thr-Gln-Tyr-Pro -Pro-Tyr-Thr-Pro-Ala-), isolated from the fruits of Leonurus heterophy llus, showed patent immunosuppressive effect on human peripheral blood lymphocytes. The solution state conformation of cycloleonurinin was e xamined by high field NMR methods, distance geometry calculation and r estrained energy minimization from NMR data. Calculation using 277 dif ferent initial structures led to a uniquely determined backbone confor mation with a root mean square deviation value of 0.80 A. The backbone structure of cycloleonurinin consists of two beta-turns, a beta VI tu rn at Pro(6).Pro(7), and a beta I turn at Pro(11)-Ala(12). In addition to two transannular 4 --> 1 backbone hydrogen bonds, which constructe d two beta-turns. two intramolecular hydrogen bonds between Tyr(9)-NH and Pro(7)-CO, and between Thr(10)-NH and Tyr(8)-CO, constructing gamm a-turns, and those between Thr(3)-NH and Tyr(8)-CO, and between Ala(12 )-NH and Thr(10)-OH, were observed. (C) 1997 Elsevier Science Ltd.