Physical Organic Chemistry on the Brain

Creators: Dougherty, Dennis A.

Abstract

The challenges to obtaining chemical-scale information on the molecules of neuroscience are considerable. Most targets are complex integral membrane proteins that are not amenable to direct structural characterization. However, by combining the tools of organic synthesis, molecular biology, and electrophysiology, rational and systematic structure−function studies can be performed in what we have termed physical organic chemistry on the brain. Using these tools, we have probed hydrophobic effects, hydrogen bonding, cation−π interactions, and conformational changes associated with channel gating. The insights gained provide important guidance for drug discovery efforts targeting ion channels and neuroreceptors and mechanistic insights for the complex proteins of neuroscience.

Additional Information

© 2008 American Chemical Society. Received January 30, 2008; Publication Date (Web): April 16, 2008. Much of the work described here stems from an ongoing and fruitful collaboration with Professor Henry Lester of Caltech's Division of Biology. We have also had excellent collaborations with Dr. Sarah Lummis of Cambridge University and Prof. Richard Horn of Jefferson Medical College. Most importantly, an outstanding group of graduate students and postdocs have executed all the experiments described and have made substantial intellectual contributions to the work, and I am extremely grateful to them. Our work was supported by the NIH (NS 34407) and the California Tobacco-Related Disease Research Program of the University of California, Grant No. 16RT-0160.

	All versions	This version
Views	0	0
Downloads	0	0
Data volume	0 Bytes	0 Bytes

Physical Organic Chemistry on the Brain

Abstract

Additional Information

Additional details