Photocontrol of ionotropic glutamate receptors: New tools for chemical neurobiology

ORGN 934

Matthew Volgraf, volgraf@berkeley.edu1, Pau Gorostiza2, Stephanie Szobota2, Rika Numano2, Richard H. Kramer2, Ehud Y. Isacoff2, and Dirk Trauner, trauner@cchem.berkeley.edu3. (1) Department of Chemistry, University of California, Berkeley, 610 Latimer Hall, Berkeley, CA 94720, (2) Department of Molecular and Cell Biology, University of California, Berkeley, 270 Life Sciences Addition, Berkeley, CA CA, (3) Center for New Directions in Organic Synthesis - Department of Chemistry, University of California, Berkeley, 602 Latimer Hall, Berkeley, CA 94720-1460
General approaches for manipulating allosteric control using synthetic optical switches has been developed. These strategies target a ligand-gated ion channel of central importance in neuroscience, the ionotropic glutamate receptor (iGluR). Using structure-based design, its ubiquitous clamshell-type ligand-binding domain has been modified to create a light-activated channel, which we call LiGluR. An agonist is covalently tethered to the protein through an azobenzene moiety, which functions as the optical switch. Alternatively, non-tethered, photochromic-ligands have been developed that effectively modulate channel activity upon photoisomerization. The development and application of these tools in cellular systems will be presented.
 

Proteins, Peptides, Amino Acids, and Enzyme Inhibitors
1:00 PM-5:00 PM, Thursday, 14 September 2006 Moscone Center -- Room 131, Oral

Division of Organic Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006