Issue Date: February 5, 2007
Ralph F. Hirschmann Award in Peptide Chemistry
Sponsored by Merck Research Laboratories
Groundbreaking research on nonnatural peptides and on protein folding has been the hallmark of work done by Samuel H. Gellman, professor of chemistry and biochemistry at the University of Wisconsin, Madison. His research has set the pace in this field and is the creative inspiration for other protein scientists.
Gellman, 47, has done this by helping to create a new field of peptide research. He theorized that oligomers of β-amino acids could adopt the same specific conformations and behaviors of conventional peptides. By designing new β-peptides with well-defined folding properties, which Gellman calls "foldamers," researchers would be able to understand better how natural peptides and proteins work.
"Foldamer research has added a new dimension to peptide science, which has traditionally focused on the chemistry of β-amino acids and their oligomers and polymers," Gellman says. "Creating and studying foldamers may provide tools and strategies to address biomedically important problems."
Gellman's group and others demonstrated the utility of this approach when they created β-peptide oligomers with highly potent antibacterial activity that mimicked the performance of natural antimicrobial peptides.
Gellman's studies have also made important contributions to secondary protein structure, particularly the structure of β-sheets. His group developed a means to make short peptides that form an antiparallel β-sheet secondary structure in water. The ability to make these small, water-soluble β-sheets helped overcome the persistent problem of previous model systems that had resulted in intractable, aggregation-prone molecules. Gellman's research found that the stability of the β-sheets depended on how adjacent peptide strands were linked. By using a D-proline in the linking segments, Gellman created the first parallel β-sheets that fold in water. Related research created one of the first three-stranded β-sheets that folds in water, and Gellman demonstrated that β-sheets grow more stable as the strands are lengthened.
"The essential Sam Gellman is a colleague who thinks clearly and critically, who applies his insights to questions of fundamental significance, and who has the intellectual breadth and courage to lead the field in new directions," says colleague David A. Tirrell, division chair of chemical and chemical engineering at California Institute of Technology.
Gellman received an undergraduate degree, magna cum laude, in 1981 from Harvard University and a Ph.D. in organic chemistry from Columbia University in 1986. Gellman says he has been attracted to organic chemistry because it gives him the freedom to explore the complexity of life at the molecular level, yet it doesn't limit him to working only with the molecules that occur in living organisms. "Organic chemistry allows one to create new subjects of study, a kind of license that thrilled me ever since I came to understand it," Gellman says.
He has received a number of professional honors, including selection as a National Science Foundation Presidential Young Investigator in 1991, an Alfred P. Sloan Research fellow in 1993, and an Arthur C. Cope Scholar Award from ACS in 1997. He has served on a several research journal advisory boards and been a member of various National Institutes of Health study sections.
The award address will be presented before the Division of Organic Chemistry.
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