Synthetic PCR Mimic Could Lead to Highly Sensitive Medical, Environmental Diagnostics

Scientists have taken another leap towards realizing a new class of polymerase chain reaction (PCR) enzyme mimics, creating a path for the development of highly sensitive chemical detection technology that goes beyond nucleic acid targets.

The blueprint for constructing synthetic structures to detect and signal the presence of targets such as small molecule medical analytes (signalers of disease or bodily malfunction, such as neurotransmitters) and environmental hazards is inspired by biology and its allosteric enzymes. The technique also could be helpful in catalysis and the production of polymers, including plastics.

The research, which has the potential for higher sensitivity than that of current detection applications, was published October 1, 2010 by the journal Science. "PCR--the backbone of the biodiagnostics industry--is an enzyme that binds to a nucleic acid and changes shape, turning on a catalyst that makes copies of the nucleic acid for detection purposes,” said Chad A. Mirkin, a professor of chemistry in the Weinberg College of Arts and Sciences at Northwestern University (Evanston, IL, USA). "What if you could do that for thousands of small molecules of interest?” he said. "We'd like to be able to detect tiny amounts of targets important to medicine and the environment, opening avenues to new types of diagnostic tools, just as PCR did for the modern fields of medical diagnostics and forensics. Our new catalysts could make that possible.”

Dr. Mirkin led a team of chemists who built a synthetic structure that sandwiches the catalyst between two chemically inert layers. This triple-layer architecture allows the use of any catalyst, as it will be kept inactive, or in an "off” state, until triggered by a specific small molecule.

The enzyme mimic behaves similar to allosteric enzymes found in nature, catalysts that change shape to perform their functions. When the mimic reacts with a specific small molecule, the triple-layer structure changes shape and opens, exposing the catalyst. The resulting catalytic reaction signals the presence of the small molecule target, similar to the way PCR amplifies a single piece of DNA.

"One of our challenges as synthetic chemists has been learning to synthesize structures inspired by biology but that have nothing to do with biology other than the fact we'd like such complex functions realized in man-made systems,” said Dr. Mirkin, also director of Northwestern's International Institute for Nanotechnology.

In the study reported in Science, the researchers use an aluminum salen complex as the catalyst in the three-layer structure. The addition of chloride (the reduced form of chlorine) triggers the catalyst and starts the polymerization process. (Chloride ion binds at an allosteric binding site, distant from the active or catalytic site.) The addition of an agent that removes the chloride stops the process, but the chloride can be added back to start it again.

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