Synthesis of RNAse active site model systems using a steroid template

The evaluation of RNAse active sire model systems based on rigid steroid te mplates is described. Our preliminary work on steroid derived RNAse model s ystems showed that preorientation of guanidinium groups and one imidazole m oiety leads to active compounds. We found that within the corticosterone de rived steroid series, the C11-alpha-configurated compounds were superior to their beta-diastereomers. In order to evaluate the influence of the confor mational flexibility of the imidazole group, a flexible side chain was intr oduced at C17. The fact that this more flexible imidazole group leads to a decrease in the hydrolytic behavior of the steroid derivative further valid ates our approach of establishing a preorientated RNAse model system for an efficient RNA hydrolysis.