Switchable enzyme/DNAzyme cascades by the reconfiguration of DNA nanostructures.

Mimicking cellular transformations and signal transduction pathways by means of biocatalytic cascades proceeding in organized media is a scientific challenge. We describe two DNA machines that enable the "ON/OFF" switchable activation and deactivation of three-component biocatalytic cascades. One system consists of a reconfigurable DNA tweezers-type structure, whereas in the second system the catalytic cascade proceeds on a switchable DNA clamp scaffold. The three-component catalytic cascades consist of β-galactosidase (β-Gal), glucose oxidase (GOx), and the K(+) -ion-stabilized hemin-G-quadruplex horseradish peroxidase (HRP)-mimicking DNAzyme. The hemin-G-quadruplex-bridged closed structure of the tweezers or clamp allows the biocatalytic cascades to operate (switched "ON''), whereas separation of the hemin-G-quadruplex by means of 18-crown-6-ether opens the tweezers/clamp structures, thus blocking the catalytic cascade (switched "OFF"). This study is complemented by two-component, switchable biocatalytic cascades composed of GOx and hemin-G-quadruplex assembled on hairpin-bridged DNA tweezers or clamp nanostructures.