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State-of-the-Art Chemical Libraries Help Identify New Compounds for Future Drug Research

Scientists from three Chicago-area universities have joined forces to develop new ways of building state-of-the-art chemical libraries that will help identify new compounds for future drug development and basic biomedical research.

University of Chicago chemist Sergey Kozmin is director of the new Chicago Tri-Institutional Center for Chemical Methods and Library Development.

Scientists from the University of Chicago, Northwestern University and the University of Illinois at Chicago will establish the Chicago Tri-Institutional Center for Chemical Methods and Library Development with a $9.2 million grant from the National Institutes of Health. Furthermore, the Chicago Biomedical Consortium, which is funded by the Searle Funds at the Chicago Community Trust, has awarded a $2 million Lever grant to support the core infrastructure of the center and to make its resources available to the entire Chicago scientific community.

"In order to develop new drugs, you need to start with new compounds," said Center Director Sergey Kozmin, Associate Professor in Chemistry at the University of Chicago.

Kozmin's laboratory screens compounds specifically for their ability to kill cancer cells, but the chemical libraries that the Chicago Tri-Institutional Center produces will be readily available to many biology labs across the nation. The center also will broadly test for potential use against neurodegenerative disorders, infectious diseases and other therapeutic targets.

During the last two years, Kozmin's laboratory has used parallel organic synthesis, which enabled them to perform many reactions simultaneously, to build 3,000 new molecules in his search for anti-cancer compounds. Now he and his associates have the resources to build a facility next year in the Searle Chemistry Laboratory on the University of Chicago campus that will be able to synthesize new compounds 10 times as fast.

The new center's work will focus on the synthesis of what biologists call "small molecules," Kozmin said. "Compared to large proteins, organic molecules that become drugs are rather small in size, however, such small molecules can make a big impact," he said.

Many existing drugs share similar molecular structures. Future advances in drug discovery and basic biomedical research both depend on the ability to more efficiently synthesize new compounds with significantly different molecular structures.

Working with Kozmin to establish the center were four University of Chicago colleagues: Hisashi Yamamoto, the Arthur Holly Compton Distinguished Service Professor in Chemistry; Viresh Rawal, Professor in Chemistry; Milan Mrksich, Professor in Chemistry; and Stephen Kron, Associate Professor in Molecular Genetics and Cell Biology.

Collaborating from Northwestern University is Karl Scheidt, the Irving M. Klotz Research Professor in Chemistry; and from the University of Illinois at Chicago are Vladimir Gevorgyan, Professor of Chemistry; and Jie Liang, Professor of Bioengineering.

"Each of these groups has expertise in different areas of organic chemistry," Kozmin said. "The idea is to combine this intellectual effort in order to produce these new molecules much more efficiently than anything that has been done before."

Organic chemists traditionally have collaborated with biologists while competing with other members of their own discipline who work on the same problem. "Here the idea is different," Kozmin said. "We would like to address a problem, but we would like to see how each of us can help each other in addressing that problem."

Supporting Kozmin's efforts to land the new NIH center in Chicago were Donald Levy, Vice President for Research and for National Laboratories; Robert Fefferman, Dean of the Physical Sciences Division; and Michael Hopkins, Professor and Chairman of the Chemistry Department.

"The National Institutes of Health this year funded five centers nationwide for chemical methodology and library development, four of which were renewals for existing centers. It's a great tribute to the scientific creativity and reputation of Sergey and his colleagues that their center is the only new one," Hopkins said.

"The Center will greatly bolster Chicago's stature as an emerging force in chemical biology, drug discovery and biomedicine, and will be a centerpiece of the Searle Laboratory when it reopens after renovation next spring."

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