NIGMS center grants will spice up chemical libraries

October 10, 2002

Variety has been called the spice of life and the soul of pleasure. For chemists developing combinatorial libraries, it is the ultimate goal.

These high-quality libraries of diverse chemical structures give scientists powerful tools to discover small molecules with a wide range of physiological properties. Whether scientists are looking for a new antibiotic or a small molecule to bind to a specific protein, they typically rely on screening hundreds or thousands of chemicals. Having the ability to synthesize carefully designed libraries will spare researchers the labor and expense of purifying or synthesizing individual compounds to screen.

Recognizing the need for new, high-throughput technologies to develop customized libraries, NIGMS announces support for two Centers of Excellence in Chemical Methodologies and Library Development (CMLD). Each center is a collaborative effort involving several researchers and projects. NIGMS is awarding a total of more than $5.5 million for the first year of these 5-year awards. Over their lifetime, the grants together are expected to total more than $20 million.

Directing the two new centers are:"The intent of this initiative is to attract the best academic chemists to develop a wide range of versatile, dependable, library-related methods," said Dr. Judith H. Greenberg, acting director of NIGMS. "Ready access to these new methods will give biologists, in collaboration with chemists, the ability to obtain combinatorial libraries that are tailor-made to meet their specific research needs."

According to Dr. John M. Schwab, the NIGMS chemist who spearheaded the initiative, "Combinatorial chemistry uses massively parallel synthesis to rapidly assemble libraries. We are looking for new, highly efficient methods for synthesis, separation, purification, and analysis that will accelerate the creation of libraries and enable a broader range of structures to be made."

"Another key feature of the CMLD program is that each center must be highly integrated, featuring collaborative, synergistic projects," said Schwab. "This is not typical in the academic chemistry community. But experience has shown that unique insights can be gained when scientists approach a project from different perspectives."

The initiative comes at an opportune time, because recently developed automated screening tools allow scientists to sift through massive collections of compounds in short order. This approach was quickly adopted by the pharmaceutical industry, which routinely uses it to discover bioactive compounds that potentially could be developed into new drugs. Although industry has embraced the use of combinatorial chemistry, it rarely publishes new methods for generating libraries.

Of the chemical libraries that are available to the entire scientific community, many have been assembled using a small number of methods and core chemical scaffolds. That means they contain limited variety. The NIGMS effort seeks to enable the creation of truly unique and diverse, high-quality libraries through the development of new chemical methods. That, said Schwab, "will produce lasting benefits for all of biomedical science."
-end-
For information about the new awards, contact Alisa Machalek in the NIGMS Office of Communications and Public Liaison at 301-496-7301 to speak with NIGMS chemist and program director Dr. John Schwab.

NIH/National Institute of General Medical Sciences

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