DNA Helix-Stack Switching as the Basis for the Design of Versatile Deoxyribosensors

The charge conduction properties of DNA can be harnessed for monitoring the binding of a ligand to its receptor. Two classes of such DNA-based sensors (deoxyribosensors) have been described for the ligand adenosine, each generated by the functional coupling of an adenosine-specific DNA aptamer to a charge-conductive DNA path. Here, we report a systematic investigation of the extent to which the features of such ligand-specific deoxyribosensors can be made universal. We have exploited established rules for DNA helical stacking within three-way helical junctions to design and characterize the properties of deoxyribosensors specific for the amino acid derivative, argininamide. The biochemical detection methods described here should translate easily to direct and rapid measurements of changes in current flow using chip-based methods. The results presented here suggest general directions for the design and assembly of deoxyribosensors specific for any molecular ligand, and describe a novel methodology for investigating helical stacking within DNAs and RNAs of unknown tertiary folding, such as novel ribozymes and deoxyribozymes.