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Gary L. Grunewald, Ph.D.

Dr. Gary Grunewald is a Professor of Medicinal Chemistry at the University of Kansas. He obtained undergraduate degrees in both chemistry and pharmacy at Washington State University where he was elected to membership in Phi Beta Kappa. He received a Wisconsin Alumni Research Foundation Fellowship and an NIH Predoctoral Fellowship for his graduate work at the University of Wisconsin. His Ph.D. dissertation (with Howard Zimmerman) described the chemistry of barrelene and included the photochemical conversion of barrelene to semibullvalene, the first recognized example of the di-p-methane rearrangement. He then joined (1966) the faculty at the University of Kansas in the Department of Medicinal Chemistry where he has been ever since. He served as department chair in 1994-2003. He received the Higuchi/Simons Research Achievement Award for research excellence in the biomedical sciences at the University of Kansas. His research has concentrated on mechanistic studies of neurotransmitters and drugs affecting them in the central nervous system employing most of the techniques of drug design (conformationally defined (rigid) analogs, QSAR, molecular modeling, site-directed mutagenesis and structure-based drug design using protein crystallography). He has had the good fortune of working with a number of excellent senior collaborators and with a wonderful group of undergraduate, graduate and postdoctoral students. In studies of conformation-activity relationships his group showed that that amphetamine had one optimal conformation for inhibition of the reuptake of catecholamine neurotransmitters but had a different optimal conformation for causing vesicular release of the same neurotransmitter in presynaptic neurons. His group was able to explain why homozimeldine retained the selectivity for the serotonin transporter over the norepinephrine transporter that its parent zimeldine displayed and also explained, through molecular mechanics calculations, why homozimeldine was less potent than the parent zimeldine. Recent work has concentrated on finding a potent and selective inhibitor of epinephrine biosynthesis to explore the poorly understood role of epinephrine in the central nervous system. Through use of rigid analogs they showed that phenylethylamines bind to the enzyme in a fully extended conformation and they confirmed the reality of this conclusion using transferred nuclear Overhauser enhancements to determine the torsion angles of the flexible ligand 3,4-dichloroamphetamine when bound to the enzyme. They have shown that a careful combination of steric factors and pKa control using ß-fluorination (an example of the Goldilocks Effect) can result in a potent inhibitor of phenylethanolamine N-methyltransferase that shows extremely low affinity for the competing binding site, the α2-adrenoceptor. Through a combination of nmr studies and quantum chemical calculations, they were able to accurately predict the relative stereochemistry of six of the seven chiral centers in epothilone before the x-ray crystal structure of this anticancer drug was known. 

He has served the Medicinal Chemistry Division of ACS as a member of the Long Range Planning Committee (1991-1994), as Vice Chair (1993), Chair (1994) and Councilor (1999-2001). He served as general chair of the 27th National Medicinal Chemistry Symposium in 2000. He served as Chair of the Research Committee (1983-85) and as a member of the Board of Directors (1980-1991) of the Kansas Affiliate of the American Heart Association He also served as Chair of the Medicinal Chemistry and Pharmacognosy Section of the Academy of Pharmaceutical Sciences (1983) and as Chair of the Pharmaceutical Sciences Section of the American Association for the Advancement of Science (1994). He serves on the Editorial Advisory Boards for Bioorganic and Medicinal Chemistry and Bioorganic and Medicinal Chemistry Letters. He was elected as a Fellow of both the AAPS (2006) and AAAS (1992).

ACS Division of Medicinal Chemistry

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