Gilman Lecture in Chemistry: Dennis A. Dougherty
|Date/Time:||Thursday, 08 Apr 2010 at 8:30 pm|
|Location:||1352 Gilman Hall|
|Channel:||College of Liberal Arts and Sciences|
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The initial chemical event of nicotine addiction involves nicotine binding to and activating acetylcholine (ACh) receptors in the brain. ACh receptors, like most of the signaling molecules of the brain, are complex, integral membrane proteins that are resistant to the standard tools of structural biology and biochemistry. As such, chemistry provides the most powerful tool for unraveling the structures and functions of the molecules of memory, thought, and sensory perception and of Alzheimer's, Parkinson's and schizophrenia. Using the mindset and methodologies of physical organic chemistry, and combining them with molecular biology, electrophysiology and computer modelling, we have probed these complex membrane proteins with a precision and subtlety normally associated with small molecule studies. We have discovered key hydrogen bonding interactions that contribute to binding of drugs to ACh receptors. Most significantly, we have established that the cation-π interaction plays a pivotal role in promoting the high potency of nicotine in the brain, leading to its addictive properties.
Professor Dennis A. Dougherty received his B.S. and M.S. degrees from Bucknell University in 1974. He did his doctoral research at Princeton University with Kurt Mislow and a year of post-doctoral studies with Jerome Berson at Yale University. Dougherty joined the faculty in the Division of Chemistry and Chemical Engineering at the California Institute of Technology in 1979, where he is now the George Grant Hoag Professor of Chemistry.
Dougherty is perhaps best known for development of the cation-π interaction, a novel but potent binding interaction between molecules that plays a central role in establishing protein structures and in modulating drug-receptor interactions. The fundamental nature of the interaction was established through extensive theoretical and model studies by the Dougherty group. Dougherty also established the prevalence of the cation-π interaction in biological systems, and it is now recognized to be important in a wide range biological processes. More recently, Dougherty has addressed molecular neurobiology, applying the mindset and tools of physical organic chemistry to the complex proteins of neuroscience - the molecules of memory, thought, and sensory perception and of Alzheimer's, Parkinson's and schizophrenia. Target receptors include the nicotinic acetylcholine receptor, the 5-HT3 (serotonin) receptor and the D2 dopamine receptor. Through these efforts, Dougherty has produced fundamental insights into drug-receptor interactions, including cation-π interactions.
Dougherty has been recognized with a number of awards, including the ACS James Flack Norris Award for Physical Organic Chemistry, the AstraZeneca Excellence in Chemistry Award, the Arthur C. Cope Scholar Award, and has been recognized as a Javits Neuroscience Investigator by NIH. He is a member of the National Academy of Sciences and a fellow of the American Association for the Advancement of Science and the American Academy of Arts and Science. He is also the co-author, with Professor Eric Anslyn, of the influential textbook, "Modern Physical Organic Chemistry."