New Tools for Drug Discovery

The painstaking nature of medicinal chemistry contributes to the time and cost of drug development. In fact, the number of new drug and biologic applications submitted to the Food and Drug Administration (FDA) has significantly declined in recent years.

In a report released earlier this year, the FDA calls for a new toolkit specifically “to improve predictability and efficiency along the critical path from laboratory concept to commercial product.” In typical Rensselaer fashion, professors Jonathan Dordick and Curt Breneman are employing new technologies to furnish that toolkit.

To improve efficiency, Dordick, the Howard P. Isermann ’42 Professor of Chemical and Biological Engineering at Rensselaer, says, “We’re looking at making a paradigm shift in how drug discovery and drug development are performed.”

Dordick has spent the past 15 years harnessing the power of enzymes, biological molecules that catalyze chemical reactions, to produce unique chemical structures. He calls the process combinatorial biocatalysis, a term that merges his biotechnological approach with the industry standard of combinatorial chemistry.

Dordick says combinatorial chemistry is very good “if you’re starting from basic building blocks and putting them together.” But once you have a structure of interest, called a “lead molecule,” organic chemistry methods lose their efficiency. Generating a series of analogs in deliberate ways is presently a major bottleneck in the development process, says Dordick.

“Combinatorial biocatalysis presents a possibility to dramatically accelerate that,” says Dordick. “Because biocatalysis can allow single step transformations on complex molecules, unlike more traditional synthetic chemistry, and can do this with exquisite selectivity, the opportunity to optimize lead candidates quickly and efficiently can now become a reality. This should make a major dent in overcoming the current bottleneck in the preclinical phase of drug development.”

To use biocatalysis as a drug discovery tool requires development of “enabling capabilities,” says Dordick. The National Institutes of Health (NIH) is funding that very enterprise through a Bioengineering Research Partnership Grant.

The four-year, $2.7 million grant was awarded to a team that is led by Dordick and includes researchers from the University of California-Berkeley, Massachusetts Institute of Technology, and Oak Ridge National Laboratory.