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Jonathan Dordick and Shekhar Garde

(l-r) Jonathan Dordick and Shekhar Garde are part of a team working to develop drugs faster and more economically. Photo by Mark McCarty

Chemical and Biological Engineering

New Tools for Drug Discovery

The National Institutes of Health has awarded a Rensselaer research team a $2.7 million, four-year grant to develop new tools for drug discovery.

The grant, awarded in partnership with the University of California, Berkeley, Massachusetts Institute of Technology, and Oak Ridge National Laboratory, will support basic research intended to produce effective pharmaceuticals faster and more economically.

“This is a stellar partnership that relies on many different skill sets,” says Jonathan Dordick, Rensselaer’s Howard P. Isermann ’42 Professor of Chemical and Biological Engineering, who is heading the research team that also includes Shekhar Garde, assistant professor of chemical and biological engineering at Rensselaer. “Our goal is to develop a key set of tools to synthesize and screen promising compounds rapidly, and identify those most suitable for further development as potential new drugs.”

Recent advances in chemistry and screening techniques make it possible to identify large numbers of promising compounds, known as derivative libraries.

Yet, the subsequent testing required to evaluate each compound is expensive and slow, bottlenecking drug development.

Dordick’s team is proposing a novel set of techniques that will remove this bottleneck. “With this research,” he says, “we will be able to generate completely new compounds, accessing a whole new range of molecules and expanding molecular libraries.”

To produce the derivative libraries, the researchers will use enzymes to react with promising compounds attached to small beads or soluble polymer supports.

Because the products of the enzymatic reactions remain on the bead or polymer, further derivatization is possible by simply washing away the initial reagents and adding in new ones. It is hoped this will enable rapid and repeated synthesis of compound derivatives.

The researchers will begin work with a series of simple compounds and progress to complex natural products, including the flavonoid bergenin, and current pharmaceuticals, including the current HIV-1 protease inhibitor indinavir.

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Rensselaer Magazine: Summer 2004
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