Professor Dexter B. Northrop received his B.A. degree in chemistry from St. Olaf College in 1962 and his Ph.D. in biochemistry from Case Western Reserve in 1968. He did postdoctoral studies in the Medical School of Harvard University and in the Biochemistry Department of the University of Wisconsin. He joined the faculty of the University of Wisconsin School of Pharmacy as an Assistant Professor in 1971. He was promoted to Associate Professor in 1976 and to the rank of Professor in 1982. He served as the Chair of the Biochemistry and Medicinal Chemistry Division from 1989 to 1995.
Professor Northrop’s research interests are in enzyme kinetics. As a graduate student, he discovered the first cobalt metalloenzyme, formulated and documented the last of the four general mechanisms recognized today in steady-state enzyme kinetics, determined the first kinetic patterns involving isotopic exchange reactions, and performed the second Paramagnetic Nuclear Magneto Resonance spectral assay for substrate binding to an enzyme active site. As a postdoctoral student he performed the first spectral titration of a metalloenzqme using Magneto Optical Rotatory Dispersion, and developed the first multiple inhibition diagnostic to determine the order of product release in enzyme kinetics. As an assistant professor he derived the equations for the expression of isotope effects within steady-state kinetics of enzyme-catalyzed reactions that provided an operative nomenclature for the field and have since become one of the cornerstones of mechanistic enzymology. At that time he also developed the methods for extraction and purification of bacterial enzymes responsible for resistance to aminoglycoside antibiotics. Several such enzymes were purified, their kinetic mechanisms established, and their structure/activity relationships determined for antibiotic substrates and inhibitors as a prelude to seeking new antibiotics that would combat resistance. (The latter never materialized due to NIH funding cuts in 1983 for antibiotic research, but others are now citing these works and following this lead after a twenty year lull.)
Professor Northrop then turned his attention to aspartic proteases and solved their kinetic and chemical mechanisms, which happened to answer the oldest question in mechanistic enzymology (i.e. what is the origin of the anomalous acidic pH profile of pepsin, published in 1908) and led to a WARF-sponsored patent for a new method of drug discovery to combat AIDS and Alzheimer’s diseases, among others, which depend on specific aspartic proteases. Finally, in the past decade, he developed the field of enzyme kinetics at high hydrostatic pressure by combining pressure effects with isotope effects. This unique combination enabled the first assignments of volume changes to specific steps of enzymatic catalysis. Notable in this effort was the documentation of pressure dependence for a heavy atom isotope effect. This surprising result reveals the origin of rate acceleration in enzyme catalyzed reasons to be different from anything described by semi-classical transition-state theory or physical organic chemistry. It presents enzymologists with a major paradigm shift that was recently the center of attention at a national meeting in California and an international meeting in London. With new enzymes being identified almost daily by modern proteomics as potential drug targets, understanding how enzymes work is increasingly important to drug discovery and drug development.
Professor Northrop plans to retire on July 5, 2006 after completing more than 35 years service as a teacher and researcher. The Executive Committee of the School of Pharmacy commends Professor Northrop as fully deserving of the honorary emeritus status for his fundamental contributions to enzymology and drug design.