Rensselaer awarded $2.7 million NIH grant to improve drug development process

03/01/04

TROY, N.Y. -- The National Institutes of Health (NIH) has awarded Rensselaer Polytechnic Institute 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 (MIT), and Oak Ridge National Laboratory, will support basic research intended to produce effective pharmaceuticals faster and more economically.

Jonathan Dordick, the Howard P. Isermann '42 Professor of Chemical and Biological Engineering at Rensselaer, leads the research team that includes Shekhar Garde, assistant professor of chemical and biological engineering at Rensselaer; Alexander Klibanov, professor of chemistry and bioengineering at MIT; Douglas Clark and Jeffrey Reimer, professors of chemical engineering at U.C. Berkeley; and Brian Davison, director of life sciences at Oak Ridge.

"This is a stellar partnership that relies on many different skill sets to complete the research," Dordick said. "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." The current process of developing a single new therapeutic drug can take many years and cost up to $1.7 billion, according to a recent report in Chemical & Engineering News.

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. The resulting bottleneck in drug development has attracted considerable attention among researchers seeking to advance more efficient and affordable processes.

Dordick and the team are proposing a novel set of techniques that will, if successful, remove this bottleneck. "With this research," Dordick said, "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. However, to achieve this novel synthetic strategy, Dordick and the research team will need to obtain a fundamental understanding of how enzymes function with their reactants attached to a bead, and then identify ways to coax enzymes into working better under such conditions. "Successful completion of this research program will result in a powerful new tool that biomedical investigators can use to speed the search for new, more potent therapeutics," Dordick said.

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.

This award represents Rensselaer's first Bioengineering Research Partnership Grant from NIH. Rensselaer currently has 30 active grants from the NIH totaling $24 million, an increase in five years from three active NIH grants totaling $600,000. The basic research supported by this grant will be carried out in the new Rensselaer Center for Biotechnology and Interdisciplinary Studies, a state-of-the-art facility scheduled to open in September 2004.

Source: Eurekalert & others

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