Serotonin (5-HT) is a neurotransmitter that has been implicated in the aetiology of numerous Mental Health disorders, including depression, anxiety, social phobia, schizophrenia, obsessive-compulsive and panic disorders, migraine, and eating disorders. There are 12 5-HT receptor subtypes with similar recognition properties yet widely divergent physiological roles that belong to the same family of G Protein Coupled Receptors (GPCRs), hindering the discovery of subtype-selective drugs. Knowledge of the 3-dimensional structure of these receptors would enable the design of selective drugs. However, solving the structure at atomic resolution of membrane proteins such as GPCRs has been hampered by the difficulty to purify sufficient amounts of homogeneous and functional protein. Here, it is proposed a novel, proprietary expression system combined with a purification method to generate large amounts of high quality purified receptor, which could solve the bottleneck for structural elucidation of these important drug targets. Our goal is to generate large amounts of purified homogenous receptor sample for each one of the 12 human 5-HT receptor subtypes. This high quality purified material will be a highly valuable product enabling structural elucidation of these receptors.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
7R44MH068919-04
Application #
7301123
Study Section
Special Emphasis Panel (ZRG1-MDCN-L (10))
Program Officer
Grabb, Margaret C
Project Start
2003-08-01
Project End
2008-05-31
Budget Start
2006-12-06
Budget End
2007-05-31
Support Year
4
Fiscal Year
2006
Total Cost
$288,061
Indirect Cost
Name
Polgenix, Inc.
Department
Type
DUNS #
785024089
City
Cleveland
State
OH
Country
United States
Zip Code
44106
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Lodowski, David T; Salom, David; Le Trong, Isolde et al. (2007) Crystal packing analysis of Rhodopsin crystals. J Struct Biol 158:455-62
Lodowski, David T; Salom, David; Le Trong, Isolde et al. (2007) Reprint of ""Crystal packing analysis of Rhodopsin crystals"" [J. Struct. Biol. 158 (2007) 455-462]. J Struct Biol 159:253-60