Document Detail

Photoproteins: important new tools in drug discovery.
MedLine Citation:
PMID:  19035847     Owner:  NLM     Status:  MEDLINE    
The G protein-coupled receptor (GPCR) family is a major target for drug discovery, and most, if not all, GPCRs can couple to Ca2+ signaling. Consequently, there are a number of cellbased, primary, high-throughput screening (HTS) assays used for drug discovery that assess changes in intracellular Ca2+ as a functional readout of GPCR activation. Historically, changes in intracellular Ca2+ levels have been readily detected using fluorescent dyes that emit light in proportion to changes in intracellular Ca2+ concentration. An alternative approach to indirectly measure changes in Ca2+ concentrations involves the use of recombinantly expressed biosensor photoproteins, of which aequorin is a prototypic example. These biosensors have the advantage that they provide an intense luminescent signal in response to elevations in intracellular Ca2+. This exquisite sensitivity, the high signal-to-noise ratios, and the ability to target expression to discrete subcellular sites (in order to detect Ca2+ microdomains) have made photoproteins a principal choice in a wide range of GPCR drug discovery programs. Photoproteins are also finding increasing use in detecting activation of other molecular target classes such as ligand-gated ion channels and transporters. This review focuses upon the use of calcium photoproteins principally for use in GPCR drug discovery and HTS.
Richard M Eglen; Terry Reisine
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Assay and drug development technologies     Volume:  6     ISSN:  1540-658X     ISO Abbreviation:  Assay Drug Dev Technol     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-11-27     Completed Date:  2009-03-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101151468     Medline TA:  Assay Drug Dev Technol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  659-71     Citation Subset:  IM    
Bio-discovery, PerkinElmer Life and Analytical Sciences, Waltham, MA 02451, USA.
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MeSH Terms
Calcium / metabolism
Calcium Signaling / genetics,  physiology
Drug Design
Fluorescent Dyes
Luminescent Proteins / genetics*,  physiology*
Pharmacology / trends*
Receptors, G-Protein-Coupled / genetics,  physiology
Reg. No./Substance:
0/Fluorescent Dyes; 0/Luminescent Proteins; 0/Receptors, G-Protein-Coupled; 7440-70-2/Calcium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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