CONFORMATIONAL-ANALYSIS OF THIOSEGETALINS BY DISTANCE GEOMETRY CALCULATION

Three-dimensional structures in DMSO-d(6) of cyclic thiopeptides, thio -segetalins A2, B1 and B2, prepared from segetalins A and B, were dete rmined by distance geometry calculation and restrained energy minimiza tion from NMR data. The backbone structure of thiosegetalin A2, consis ting of two beta-turns, a beta II turn at Trp(5)-Ala(6) and a beta VI turn at Val(2)-Pro(3), retains the backbone conformation of segetalin A, both of which showed estrogen-like activity. Whereas, the backbone conformations of cyclic pentapeptides, thiosegetalins B1 and B2 were d ifferent from that of the parent compound, segetalin B. The backbone c onformations are important for segetalins to show estrogenic activity. Though thionation is a minimal variation of isosteric replacement, it is a useful conformational modification of cyclic peptides.