Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Click here to register for free online access

Sign In to gain access to subscriptions and/or personal tools.
Journal of Biomolecular Screening
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
1087057106298637v1
12/3/312    most recent
Right arrow References
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (2)
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Peters, M. F.
Right arrow Articles by Scott, C. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Peters, M. F.
Right arrow Articles by Scott, C. W.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Evaluation of Cellular Dielectric Spectroscopy, a Whole-Cell, Label-Free Technology for Drug Discovery on Gi-Coupled GPCRs

Matthew F. Peters

Lead Generation, AstraZeneca Pharmaceuticals LP, Wilmington, DE, Matt.Peters{at}astrazeneca.com

Katharine S. Knappenberger

Neuroscience Biology Departments, AstraZeneca Pharmaceuticals LP, Wilmington, DE

Deidre Wilkins

Lead Generation, AstraZeneca Pharmaceuticals LP, Wilmington, DE

Linda A. Sygowski

Neuroscience Biology Departments, AstraZeneca Pharmaceuticals LP, Wilmington, DE

Lois Ann Lazor

Lead Generation, AstraZeneca Pharmaceuticals LP, Wilmington, DE

Jianwei Liu

Neuroscience Biology Departments, AstraZeneca Pharmaceuticals LP, Wilmington, DE

Clay W. Scott

Lead Generation, AstraZeneca Pharmaceuticals LP, Wilmington, DE

Cellular dielectric spectroscopy (CDS) is an emerging technology capable of detecting a range of whole-cell responses in a label-free manner. A new CDS-based instrument, CellKey, has been developed that is optimized for G-protein coupled receptor (GPCR) detection and has automated liquid handling in microplate format, thereby making CDS accessible to lead generation/optimization drug discovery. In addition to having sufficient throughput, new assay technologies must pass rigorous standards for assay development, signal window, dynamic range, and reproducibility to effectively support drug discovery SAR studies. Here, the authors evaluated CellKey with 3 different Gi-coupled GPCRs for suitability in supporting SAR studies. Optimized assay conditions compatible with the precision, reproducibility, and throughput required for routine screening were quickly achieved for each target. Across a 1000-fold range in compound potencies, CellKey results correlated with agonist and antagonist data obtained using classical methods ([ 35S]GTP{gamma}S binding and cAMP production). For partial agonists, relative efficacy measurements also correlated with GTP{gamma}S data. CellKey detection of positive allosteric modulators appeared superior to GTP{gamma}S methodology. Agonist and antagonist activity could be accurately quantified under conditions of low receptor expression. CellKey is a new technology platform that uses label-free detection in a homogeneous assay that is unaffected by color quenching and is easily integrated into existing microtiter-based compound testing and data analysis procedures for drug discovery. (Journal of Biomolecular Screening 2007:312-319)

Key Words: cellular dielectric spectroscopy • GPCR • GTP{gamma}S binding

This version was published on April 1, 2007

Journal of Biomolecular Screening, Vol. 12, No. 3, 312-319 (2007)
DOI: 10.1177/1087057106298637
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 J Biomol ScreenHome page
M. F. Peters and C. W. Scott
Evaluating Cellular Impedance Assays for Detection of GPCR Pleiotropic Signaling and Functional Selectivity
J Biomol Screen, March 1, 2009; 14(3): 246 - 255.
[Abstract] [PDF]