Expanding the catalytic repertoire of ribozymes and deoxyribozymes beyond RNA substrates.

Abstract

The catalytic role of ribozymes in RNA processing is well established. However, the proposal that ribozymes can be discovered by in vitro selection has resulted in the identification of a relatively small number of novel ribozyme catalysts. The limited repertoire of the native functional groups of RNA and its inherent instability have led to the hypothesis that ribozymes that contain non-natural functional groups (ie, modified nucleic acids) would provide greater catalytic activity toward non-RNA substrates. Moreover, because of their greater stability, reduced cost and ease of synthesis, native and modified deoxyribozymes have recently dominated the in vitro selection of enzymes that catalyze reactions involving non-RNA substrates. Deoxyribozymes bind easily to metal cofactors and provide a scaffold for templating chemical reactions, representing two significant advantages of deoxyribozymes compared with ribozymes for the catalytic transformation of non-RNA substrates. In addition, RNA processing illustrates the natural functions and limitations of ribozymes that have led to the shift in the emphasis of research from ribozymes to deoxyribozymes.