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.
About Biotechnology at Rensselaer
Biotechnology research at Rensselaer comprises multidisciplinary work, combining life sciences, information science, applied mathematics, engineering, and physics. Areas of research include biocatalysis and metabolic engineering (application of enzymes and manipulated metabolic pathways); functional tissue engineering (creating replacement tissues and organs that can augment or replace damaged tissue); integrated systems biology (systems-based, experimental methods of gaining insight into the function of complex biosystems); and computational biology and bioinformatics (using information technology tools to search massive databases, such as those generated by the Human Genome project, to efficiently correlate relevant facts).
About Rensselaer
Rensselaer Polytechnic Institute, founded in 1824, is the nation's oldest technological university. The school offers degrees in engineering, the sciences, information technology, architecture, management, and the humanities and social sciences. Institute programs serve undergraduates, graduate students, and working professionals around the world. Rensselaer faculty are known for pre-eminence in research conducted in a wide range of research centers that are characterized by strong industry partnerships. The Institute is especially well known for its success in the transfer of technology from the laboratory to the marketplace so that new discoveries and inventions benefit human life, protect the environment, and strengthen economic development.