The Sigma-2 receptor is a unique protein found in most mammalian tissues. Sigma-2 receptors play an important role in growth regulation in normal cells and tumor cells of neuronal and non neuronal origin. The Sigma-2 receptor has not been purified or cloned. This grant proposal is directed at purification and cloning of the Sigma-2 receptor. This goal will be accomplished through two alternate and complementary approaches.
Specific Aim 1 is entitled: Purification, Identification and Cloning of the Sigma-2 receptor using a """"""""Click Chemistry"""""""" approach.
Specific Aim 2 is entitled: Identification and cloning of the Sigma-2 receptor using an In Silico approach. Characterization of the Sigma-2 receptor is the initial step leading to a basic understanding of the role of the Sigma-2 receptor in regulation of neuronal and non-neuronal cell function and for potential therapeutic strategies to treat drugs of abuse and/or aberrant cell growth. .

Public Health Relevance

The sigma-2 receptor is a mammalian protein in the central nervous system and in peripheral organs that may be involved in drug addiction. Sigma-2 receptors play an important role in growth regulation in normal cells and in tumor cells of different origins. Despite the presence of numerous molecular biology tools, the sigma-2 receptor has managed to evade all cloning attempts to date. This project is directed at purification and identification of the sigma-2 receptor.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21DA027191-02
Application #
7894935
Study Section
Synthetic and Biological Chemistry B Study Section (SBCB)
Program Officer
Hillery, Paul
Project Start
2009-08-01
Project End
2011-07-31
Budget Start
2010-08-01
Budget End
2011-07-31
Support Year
2
Fiscal Year
2010
Total Cost
$222,750
Indirect Cost
Name
University of Wisconsin Madison
Department
Pharmacology
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
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Guo, Lian-Wang; Hajipour, Abdol R; Karaoglu, Kerim et al. (2012) Development of benzophenone-alkyne bifunctional sigma receptor ligands. Chembiochem 13:2277-89
Hajipour, Abdol R; Guo, Lian-Wang; Pal, Arindam et al. (2011) Electron-donating para-methoxy converts a benzamide-isoquinoline derivative into a highly Sigma-2 receptor selective ligand. Bioorg Med Chem 19:7435-40