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November 7, 2002

Chemical library of molecules funded

One of the more time-consuming tasks scientists face in discovering new pharmaceuticals and other chemicals is creating compounds prior to testing. Pitt will give researchers across the country a head start by creating a chemical library of more than 50,000 molecules through a five-year, $9.6 million grant from the National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health (NIH).

Pitt’s Center of Excellence in Chemical Methodologies and Library Development is one of the first two in the country; Boston University will house the other center.

“Typically, scientists rely on a screening process when searching for small molecules that have a specific function,” says Peter Wipf, professor in Pitt’s Department of Chemistry and director of the new center. “For example, hundreds or even thousands of compounds are examined when looking for a new antibiotic or a compound that changes color quickly when exposed to a nerve gas. Having a carefully designed library available will spare researchers considerable labor and expense.”

Newly created chemicals could be used in health-related and technological advancements, including applications in drug discovery, veterinary products, agriculture, biosensors and chemical separations.

In addition, the NIGMS wants the centers to create and evaluate methods of generating chemical libraries.

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

According to 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.”

Pitt’s center will develop methods to create synthetic relatives of natural products and biomolecules, develop technology for automating and accelerating production, and discover new materials to separate compounds. A centralized facility of the center, the Diversity-Oriented Synthesis (DOS) Core, will provide access to state-of-the-art automated equipment and perform the large-scale library syntheses.

Pitt’s center also will explore peptide mimetics. Peptides show promise in many medicinal areas, including cancer immunotherapy. But drawbacks, such as the inability of the human body to absorb them orally, have caused many researchers to explore modified peptides, or mimetics, which have many of the same therapeutic properties.

N. John Cooper, dean of Pitt’s Faculty and College of Arts and Sciences, said the NIGMS grant validates the quality of the combinatorial chemistry program at Pitt.

Chemistry department researchers involved in the project include Kay Brummond, associate professor and vice director of the center; Dennis Curran, Distinguished Service Professor of Chemistry and Bayer Professor; Scott Nelson, associate professor, and Stephen Weber, professor and director of graduate studies.

Other researchers include John Lazo, Allegheny Foundation Professor and chair of pharmacology in the School of Medicine, and Billy W. Day, associate professor in the Department of Chemistry and the Department of Pharmaceutical Sciences and director of the Proteomics Core in the Schools of the Health Sciences.

Filed under: Feature,Volume 35 Issue 6

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