Analysis of conformational equilibria in aplidine using selective excitation 2D NMR spectroscopy and molecular mechanics/dynamics calculations.

Aplidine (dehydrodidemnin B), a natural product with potent antitumor activity currently in multicenter phase II clinical trials, exists in DMSO as a mixture of four slowly interconverting conformations in a ratio of 47:33:13:7. NMR spectroscopy shows that these arise as a consequence of cis/trans isomerization about the NMe-Leu(7)-Pro(8) and Pro(8)-Pyr amide bonds of the molecule's side chain. Two major conformations account for 47% and 33% of the total population, a ratio of 60:40 between the two.

Solution structure of the antitumor candidate trunkamide A by 2D NMR and restrained simulated annealing methods.

Trunkamide A (1) is a cyclic heptapeptide extracted from the ascidian Lissoclinum sp. and has shown very promising cytotoxic activity. This compound incorporates several of the motifs commonly observed in the Patellin family, including dimethylallyl (Dma) Thr and Ser side chains and a thiazoline heterocycle.