Solution state conformation of an immunosuppressive cyclic dodecapeptide, cycloleonurinin

Abstract

Abstract The cyclic dodecapeptide, cycloleonurinin, cyclo(-Gly-Pro-Thr-Gln-Tyr-Pro-Pro-Tyr-Tyr-Thr-Pro-Ala-), isolated from the fruits of Leonurus heterophyllus, showed potent immunosuppressive effect on human peripheral blood lymphocytes. The solution state conformation of cycloleonurinin was examined by high field NMR methods, distance geometry calculation and restrained energy minimization from NMR data. Calculation using 277 different initial structures led to a uniquely determined backbone conformation with a root mean square deviation value of 0.80 A. The backbone structure of cycloleonurinin consists of two β-turns, a β VI turn at Pro6-Pro7, and a β I turn at Pro11-Ala12. In addition to two transannular 4 → 1 backbone hydrogen bonds, which constructed two β-turns, two intramolecular hydrogen bonds between Tyr9-NH and Pro7-CO, and between Thr10-NH and Tyr8-CO, constructing γ-turns, and those between Thr3-NH and Tyr8-CO, and between Ala12-NH and Thr10-OH, were observed.