The hydrolysis and/or formation of phosphodiester bonds is of central importance in biology. Enzymes such as polymerases, recombinases, topoisomerases, reverse transcriptases, and others catalyze phosphoryl transfer reactions efficiently under physiological conditions. Studies of enzymological reaction mechanisms using biochemical techniques or synthetic models is currently an area of intensive interest. One extremely common but little studied enzyme mechanistic motif involves the use of two metal ions in the hydrolysis of phosphodiesters and other substrates. This proposal describes the development of selective catalysts for DNA hydrolysis that utilize this mechanistic motif. The compounds will be used to test hypotheses about enzyme mechanisms as well as for applications in biotechnology.
