ORGN 36 |
| While the human brain is arguably the most complex object on earth, the principles of physical organic chemistry can be successfully applied to garner important insights into the structure and function of the molecules of memory, thought, and sensory perception; the molecules Alzheimer's, Parkinson's, schizophrenia, and addiction. By incorporating unnatural amino acids site-specifically into neuroreceptors and ion channels, high precision information on drug-receptor contacts and molecular signaling mechanisms can be obtained. In the Cys-loop family of neurotransmitter-gated ion channels, typified by the nicotinic acetylcholine receptor, a cation-π interaction has been shown to play an important role in binding several agonists to their cognate receptor. Interestingly, though, the site of the cation-π interaction is variable, even among very closely related receptors. The cation-π interaction also plays a pivotal role in the molecular mechanisms underlying nicotine addiction. While the nicotine receptors of the peripheral nervous system (at the neuromuscular junction) are relatively insensitive to nicotine, the drug is, of course, quite potent in the brain. We have found that a cation-π interaction is the distinguishing feature that makes the CNS receptors much more sensitive to nicotine than the peripheral receptors. |
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James Flack Norris Award in Physical Organic Chemistry: Symposium in Honor of Dennis A. Dougherty
1:30 PM-5:00 PM, Sunday, April 6, 2008 Morial Convention Center -- La Nouvelle, Blrm. C, Oral
Division of Organic Chemistry |