Issue Date: February 4, 2008
Ralph F. Hirschmann Award in Peptide Chemistry
Sponsored by Merck Research Laboratories
William F. DeGrado, the George W. Raiziss Professor of Biochemistry & Biophysics at the University of Pennsylvania School of Medicine, is well-known for his work in the synthesis, structural characterization, and biomedical application of peptides. In a broader sense, DeGrado is recognized as a pioneer in the field of protein design, where he has pursued fundamental research for nearly 30 years in both industrial and academic settings.
DeGrado, 52, earned a Ph.D. from the University of Chicago and then began a career as a research chemist at DuPont's central research and development department in 1981. In 1990, he moved to a research leader position at DuPont Merck Pharmaceutical, where, by 1994, he held the position of senior director. Two years later, DeGrado shifted to academic research by moving to the University of Pennsylvania.
His focus throughout has been on major problems in peptides, peptide mimetics, and protein design and basic protein science, endeavors in which he has published more than 250 papers.
DeGrado first began working on peptide science during his graduate studies with E. T. Kaiser, with whom he developed oxime esters as supports for solid-phase synthesis, as well as demonstrated that the amphiphilic helix is an essential feature of membrane-disrupting peptides such as melittin. DeGrado went on to explore minimalist and hierarchical approaches to protein design.
According to Samuel H. Gellman, Ralph F. Hirschmann Professor of Chemistry at the University of Wisconsin, Madison, DeGrado's research is characterized by an equal concern for design and practical application. Gellman says DeGrado's industry experience is likely to have given him a bent toward functional considerations in the lab. "I think it probably has given him more insight into application than pure academic scientists have," he says.
DeGrado says that although his initial work at DuPont focused on fundamental research that had little short-term application, growing emphasis in drug research was being placed on studying the effects of chemistry on biology and the role of peptide and protein mimetics in drug development. With the decoding of the human genome, protein and peptide chemistry moved to center stage in drug discovery and development. DeGrado agrees his approach to protein design is informed significantly by his experience as a researcher in industry. "One sees in industry how one needs to be very aggressive about science to make things happen-practical things that translate into products," he says. "My time in industry showed me how to integrate fundamental science with translational goals."
In 2002, DeGrado, along with Michael L. Klein, director of the Laboratory for Research on the Structure of Matter at the University of Pennsylvania, and Gregory N. Tew, associate professor in the polymer science and engineering department at the University of Massachusetts and a former postdoctoral fellow under DeGrado, founded PolyMedix. The company is developing foldamers and small molecules as mimics of peptides and proteins. Their first products moving into the clinic are antibiotics and heparin antagonists.
DeGrado's current research at University of Pennsylvania is focused on peptide interactions with membranes and the development of computational tools to model scaffolds useful in studying peptide-to-peptide interactions. His protein design work has extended in recent years to metalloproteins, which can be used to promote controlled catalysis in biological systems.
DeGrado says he is particularly honored by the award because of "the immense influence that Ralph Hirschmann has had on my scientific interests and development."
Perhaps DeGrado's biggest contribution has been his own leadership in peptide research. "Bill's work has been a major signpost for me," Gellman says. "Everyone who has pursued protein design, at any level, has been influenced by DeGrado's contributions."
The award address will be presented before the Division of Organic Chemistry.
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