University of California Riverside scientists have used DNA nanostructures to create spatially organized enhanced enzymatic cascades. Ian Wheeldon, Ph.D., assistant professor in the department of chemical and environmental engineering, and his group develop bioanalytical devices for applications including medical diagnostics and environmental monitoring. These devices, for example, could take the form of enzymatic pathways organized on DNA scaffolding for bioassays.
In a recent paper in American Chemical Society Catalysis, Dr. Wheeldon’s team noted DNA’s properties can be used to create precisely defined multidimensional shapes with molecular-level control over structural and chemical features, potentially allowing creation of multienzyme cascades with well-defined spatial organization.
The team investigated the interactions between enzyme substrates and DNA scaffolds using a model system of horseradish peroxidase (HRP) assembled on a nanoscale DNA triangle.
“We used [HRP] as a model system to look at a series of substrates because this enzyme oxidizes a wide range of chemically distinct substrates that are commonly used in analytical assays, and all varying in their interactions with DNA,” Dr. Wheeldon said.
He continued, “We were trying to answer the question, does DNA as a scaffold make a difference to the system? A group of us is looking at using DNA as a way to organize enzymes into a pathway, for example, an efficient pathway of three enzymatic reactions. DNA is one of the only systems where we can get down to tens of nanometers and that we can use to organize pathways.
“In determining how tightly the substrates bind to DNA, we found that those that bound tightly and those that bound weakly had no effect on catalysis, but when they bound at intermediate strength, it increased catalysis. We think this occurs because as these substrates repeatedly bind to and release from the DNA scaffold, the substrate is kept at high levels around the enzymes, thereby driving high rates of catalysis.
“We are really more enzyme than DNA people, but if we are going to use DNA as a scaffold, we need to understand what it means in terms of the rest of the system.”
With spatially controlled positioning of functional materials by self-assembly remains a key goal of nanotechnology, scientists will continue to exploit DNA’s physical and chemical properties, as well as its self-assembly in inventive ways.