Synthetic RNA-cleaving DNAzymes with three protein side chains: Amines, imidazoles, and guanidines.

The development of synthetic enzyme mimics has been a long-standing goal of bioorg. chemists. Nevertheless, a synthetic RNaseA mimic - as defined as a scaffold appended with a cationic amines and imidazoles - has remained elusive, particularly in terms of turnover. We have merged synthetic nucleotide chem. with combinatorial selection to deliver a more complete (and complex) chem. complement to the catalytic repertoire of nucleic acids. Evidence of increased catalytic potential is found in the development of Mg2+-independent RNA-cleaving DNAzymes that use three functionalities that often define the active sites of protein nucleases - namely imidazoles, amines, and guanidines. Recently we have selected DNAzymes that hydrolyze ribonucleoside linkages by virtue of protein-like functionalities that provide enhanced rate consts. and showcase how functionalized DNA can provide new synthetic catalysts that begin to capture the complexity and efficiency of natural biol. ones. [on SciFinder(R)]