Conformational analysis of dolastatin 10: an NMR and theoretical approach

A solution conformational analysis of dolastatin 10, a powerful antineoplastic agent, has been carried out by means of nmr techniques and theoretical calculations. 1H mono- and bidimensional nmr experiments, as well as 1H-13C heterocorrelated spectra, have been performed on CD2Cl2 solutions. The most interesting nmr data is a huge shielding of the aCH(25) proton of the Dov residue, suggesting the presence of an interaction between the N-terminal and the aromatic C-terminal ends of the molecule. The possibility of a head-to-tail intermolecular association having been discarded, the presence of a series of preferred folded conformation has been hypothesized. Conformational theoretical analysis supports the nmr hypothesis of a folded peptide-like molecule, and a series of possible conformers in good agreement with the experimental data have been analyzed.