Pitt Receives $9.6 Million to Develop Methods of Creating Chemical Libraries

October 10, 2002

50,000-compound chemical library to expedite drug discovery, materials research, and chemical synthesis at first of two national Centers for Excellence in new federal program

PITTSBURGH—One of the more time-consuming tasks scientists face in discovering new pharmaceuticals and other chemicals is creating compounds prior to testing. The University of Pittsburgh will give researchers across the country a head start in their work 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 to be created by NIGMS; 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."

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

"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 researchers with convenient access to state-of-the-art automated equipment and perform the actual large-scale library syntheses.

Pitt's center also will explore peptide mimetics. Peptides show promise in many medicinal areas—including cancer immunotherapy. But drawbacks, including 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 (FCAS), believes the NIGMS grant validates the quality of the combinatorial chemistry program at Pitt. "Peter Wipf and his colleagues are among the most outstanding chemists in the world. They have already placed the University of Pittsburgh at the forefront of the new era of combinatorial chemistry. Combinational chemistry will be at the center of drug discovery in the 21st century, and I am delighted that their success has been recognized by the National Institute of General Medical Sciences."

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.

Wipf also directs Pitt's Center for Combinatorial Chemistry (CCC). The dean of FCAS and the faculty in the Department of Chemistry, in collaboration with the School of Medicine, the University of Pittsburgh Cancer Institute, and the University provost, created the CCC in 1997 to take advantage of the crucial role of basic scientific research in support of this new technology.

"This early vision and the broad institutional support for the CCC was a significant element in Pitt's successful competition for the NIH-supported Center of Excellence in Chemical Methods and Library Development," says Wipf.

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