Fluorescence polarization screening for allosteric small molecule ligands of the cholecystokinin receptor

Kaleeckal G. Harikumar, Erin E. Cawston, Laurence J Miller

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The success in screening for drug candidates is highly dependent on the power of the strategy implemented. In this work, we report and characterize a novel fluorescent benzodiazepine antagonist of the type 1 cholecystokinin receptor (3-(3-(7-fluoro-1-(2-isopropyl(4-methoxyphenyl)amino)-2-oxoethyl)-2,4- dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[b][1,4]-diazepin-3-yl)ureido)benzoic acid) that can be used as a receptor ligand in a fluorescence polarization assay, which is ideally suited for the identification of small molecule allosteric modulators of this physiologically important receptor. By binding directly to the small molecule-docking region within the helical bundle of this receptor, this indicator can be displaced by many small molecule candidate drugs, even those that might not affect the binding of an orthosteric cholecystokinin-like peptide ligand. The biological, pharmacological, and fluorescence properties of this reagent are described, and proof-of-concept is provided in a fluorescence polarization assay utilizing this fluorescent benzodiazepine ligand.

Original languageEnglish (US)
Pages (from-to)394-402
Number of pages9
JournalAssay and Drug Development Technologies
Volume9
Issue number4
DOIs
StatePublished - Aug 1 2011

Fingerprint

Cholecystokinin Receptors
Fluorescence Polarization
Ligands
Benzodiazepines
Preclinical Drug Evaluations
Benzoic Acid
Cholecystokinin
Fluorescence
Pharmacology
Peptides
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Drug Discovery
  • Molecular Medicine

Cite this

Fluorescence polarization screening for allosteric small molecule ligands of the cholecystokinin receptor. / Harikumar, Kaleeckal G.; Cawston, Erin E.; Miller, Laurence J.

In: Assay and Drug Development Technologies, Vol. 9, No. 4, 01.08.2011, p. 394-402.

Research output: Contribution to journalArticle

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