Synthesis of RNAse active site model systems using a steroid template

An RNAse active site model system is described. The rigid steroid backbone is used as the template on which guanidinium and imidazole moieties, necessary for the transesterification/cleavage. are assembled. By changing the stereochemistry at C11 of 2, and varying the guanidinium side chains, active compounds 9, 11, 13, 15 with different hydrolytic behavior are obtained. Comparison of the steroid compounds clearly demonstrates that changes in the geometry can influence the cleavage reaction of RNA analogs. Furthermore, an intramolecular base can enhance the cleavage rate. The pK(a) values of the most active bis(guanidinium) compound 9 has been determined and the pH dependence of the cleavage reaction is discussed. (C) 1997 Elsevier Science Ltd.