The Silverman laboratory studies fundamental and applied aspects of the nucleic acids, DNA and RNA. We study DNA as a catalyst (deoxyribozyme) for bioorganic chemical reactions; we apply double-stranded DNA as a conformational constraint for other macromolecules; we investigate fundamental features of RNA folding and catalysis; and we develop allosteric nucleic acid enzymes (aptazymes) as sensors for practical detection of environmental toxins, pollutants, and other compounds. This presentation focuses on the development and application of DNA as a catalyst.

Nature uses RNA as a catalyst, or ribozyme, for biologically relevant reactions such as protein synthesis in the ribosome. The lack of 2'-hydroxyl groups in DNA has led to speculation that DNA should be less catalytically efficient than RNA, and no examples of natural DNA catalysts are known. Nevertheless, we and others have used in vitro selection to identify many artificial DNA catalysts, or deoxyribozymes, by starting with a large number (>1014) of random DNA sequences and searching for desired catalytic activities by individual sequences.

Our initial efforts with deoxyribozymes examined their use for ligation of two RNA substrates, with formation of either linear or 2',5'-branched RNA. Our more recent efforts have focused on expanding the scope of DNA catalysis beyond oligonucleotide substrates. We have learned how to engineer a small-molecule substrate binding site into a deoxyribozyme that ordinarily forms branched RNA. We have also identified a deoxyribozyme that creates a nucleopeptide linkage using a tyrosine side chain as a nucleophile. These and other new results will be discussed.