Conformational studies of Asterin B and C in solution by NMR .2. Conformational analysis by NMR and molecular dynamic simulations

The conformational properties of two pentapeptides Asterin B(Delta Pro - Thr - Ser - beta Phe - Abu - OMe, 1) and Asterin C(Delta Pro - Abu - Ser - beta Phe - Thr - OMe, 2), isolated from Chinese traditional medicine Aster tataricus, have been investigated by 2D - NMR and restrained molecular dynamic calculations (RMD). The solution conformation of 1 was characterized as a nonclassic beta- turn structure at(Delta Pro - Thr - Ser - beta Phe) region with an amphiphilic feature, which may be related to its antitumor activity against P388 leukemia. There is no evidence in the form of lowered amide proton temperature coefficients for direct hydrogen bonding as a primary source of turn stability. Instead, the major stabilization appears to be the hydrophobic interaction between aromatic rings (Delta Pro and beta Phe). Implications for stabilization of this unusual turn structure during the earliest events in protein folding are discussed. The conformation of 2 in solution was shown to be more flexible with multiple conformational averaging.