In vitro selection of DNA enzymes for bioorganic chemistry

The goal of this project is the development of DNA enzymes that are capable of catalyzing important bioorganic reactions such as the formation of peptide-nucleic acid conjugates and glycopeptides. The biological function of DNA in its double stranded form is restricted to the storage of genetic information. In its single stranded form, DNA can fold into far more complex structures that are capable of catalyzing different chemical transformations. Catalytic DNAs have not been found in nature; nevertheless, laboratory-created DNA enzymes continue to be discovered using in vitro selection. This approach is used to isolate DNAs with the desired catalytic activity from a pool of random-sequence nucleic acids. DNA enzymes that catalyze nearly a dozen of different types of reactions involving nucleic acid substrates have been generated. Recently, the Silverman laboratory has published extensively on the in vitro selection of DNA enzymes that have RNA ligase activity. In this project, in vitro selection will be used for the identification of DNA enzymes that catalyze important bioorganic reactions beyond RNA ligation. Deoxyribozymes are desired that (1) ligate peptides to DNA or RNA and (2) catalyze the formation of glycopeptide conjugates. The resulting oligonucleotide-peptide conjugates are anticipated to be useful for improving drug delivery systems, and the targeted glycopeptide compounds are important for both normal and pathological in vivo processes. The objectives of DNA-mediated bioorganic chemistry are to demonstrate that DNA has the potential for novel chemical and biochemical catalysis and to apply DNA enzymes in the laboratory for practical use.