Chemical transformations to explore expanded nucleic acid structure and function

Nucleic acid structure and function can be expanded in the laboratory beyond the natural repertoire. A new combinatorial method is presented to identify functionally and structurally important residues in catalytic DNA. Finding new DNAs enzymes for reactions involving small organic molecules necessitates a smart design of the selection technique. In vitro selection experiments are described to identify deoxyribozymes for fluorogenic aldol condensation reactions between a modified Fischer’s aldehyde and indoleninium derivatives. Naturally occurring aldehydes were also targeted by aldol chemistry. A new bioorthogonal aldol condensation for fluorogenic labeling of 5-formylpyridmines in DNAs and RNAs was established using indoleninium salts to generate hemicyanine-type chromophores with distinct photophysical properties. Detection of 5-formylpyrimidines has been demonstrated in proof-of-principle studies, and the labeling approach is propitious for investigating natural modified DNA and RNA samples.