Published September 1, 2005
Pehr Harbury is a biochemist who explores the structure, activity, and synthesis of proteins with the aim of developing more potent and more specific drugs for the treatment of disease. Early in his career, he focused on rational protein design, based on first-principles of amino acid structural chemistry. Most functional proteins consist of amino acid side chains attached to a protein backbone. Harbury developed a method for accurately predicting main- and side-chain structures, even for complex multimers. To demonstrate the power of his calculation, he and his colleagues synthesized proteins with unnatural, right-handed supercoiled structure and showed that they were able accurately to predict structures that had never previously existed. To improve understanding of side-chain functionality, Harbury developed an assay for testing the interaction of substrate and specific amino acids. Most recently, Harbury has introduced an efficient and effective method for using in vitro evolution to control combinatorial synthesis of small molecules. With this technique, he is able to tether to a single molecule the information needed to synthesize more of it. When combined with an instruction set many orders of magnitude larger than previous combinatorial chemical libraries and a large pool of chemical manipulations compatible with the process, Harbury's "DNA Display" technique promises vast increases in the speed, efficiency, and search space for the use of combinatorial chemistry in the development of new drugs.
Pehr Harbury received a B.A. (1987) and a Ph.D. (1994) from Harvard University. He was a postdoctoral fellow (1995-97) at the University of California, Berkeley, and is currently an associate professor in the Department of Biochemistry at Stanford University, where he has been on the faculty since 1997. His publications have appeared in such academic journals as PLoS Biology, Nature, Science, and Proceedings of the National Academy of Sciences USA.
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