Cascade reactions can be activated by organizing the relative positions of enzymes tethered to DNA nanostructures
DNA's self-assembling properties mean that it can be used as a building block to create structures for a range of nanotechnologies. Itamar Willner and colleagues at the Hebrew University of Jerusalem have now shown1 how the organization of enzymes and enzyme cofactors tethered to DNA nanostructures can control their catalytic activity.
The team pre-designed sequences of single-stranded DNA to create ladder-like strips of two adjacent hexagons of DNA. They then tethered enzymes glucose oxidase (GOx) and horseradish peroxidise (HRP) to neighbouring hexagons. This set-up allows a cascade reaction to occur, whereby a product of the GOx-catalysed reaction acts as the substrate for one catalysed by HRP. The cascade does not occur in an unorganized homogeneous system.
Willner and colleagues studied the effect that the distance between the enzymes has on the activity by creating DNA strips with rows of four linked hexagons and the enzymes tethered to the outer hexagons. The four-hexagon-scaffold system is less active, so increasing the distance decreases the activity. The team also studied an organized system with an enzyme–cofactor pair rather than two enzymes, showing that the longer the molecular anchor used to tether the cofactor to a two-hexagon strip, the higher the system's catalytic activity.
Wilner, O. I. et al. Enzyme cascades activated on topologically programmed DNA scaffolds. Nature Nanotech. 10.1038/nnano.2009.50 (2009)