| Abstract: | A detailed description of the two observed solution conformations of the pentapeptide lactone fragment of actinomycin D is presented using the distance constraints obtained from two-dimensional nuclear Overhauser enhancement spectra in combination with minimum energy calculations. Low energy conformational states that are compatible with the experimental distances are found for each of the two conformers. For one conformer, an all trans peptide bond conformer, is found with no intramolecular hydrogen bonds. For the other conformer, the D-Val-Pro and Pro-Sar peptide bonds were cis; this solution conformation is the same as that found in both the crystal structure of the pentapeptide lactone as well as of the native actinomycin D itself. These results are discussed in terms of the combined influence of conformation and the effects of mutual intramolecular association of the pentapeptide lactone moieties in native actinomycin D on its cytotoxic activity. |
