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Novel fluorescence competition assay for retinoic acid binding proteins

DOI: 10.1021/acsmedchemlett.8b00420 DOI Help

Authors: Charles W. E. Tomlinson (Durham University) , David R. Chisholm (Durham University) , Roy Valentine (High Force Research Ltd) , Andrew Whiting (Durham University) , Ehmke Pohl (Durham University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Acs Medicinal Chemistry Letters

State: Published (Approved)
Published: November 2018

Abstract: Vitamin A derived retinoid compounds have multiple, powerful roles in the cellular growth and development cycle and, as a result, have attracted significant attention from both academic and pharmaceutical research in developing and characterizing synthetic retinoid analogues. Simplifying the hit development workflow for retinoid signaling will improve options available for tackling related pathologies, including tumor growth and neurodegeneration. Here, we present a novel assay that employs an intrinsically fluorescent synthetic retinoid, DC271, which allows direct measurement of the binding of nonlabeled compounds to relevant proteins. The method allows for straightforward initial measurement of binding using existing compound libraries and is followed by calculation of binding constants using a dilution series of plausible hits. The ease of use, high throughput format, and measurement of both qualitative and quantitative binding offer a new direction for retinoid-related pharmacological development.

Journal Keywords: ATRA; fluorescence; high-throughput screening; Retinoids

Subject Areas: Chemistry, Biology and Bio-materials

Instruments: I03-Macromolecular Crystallography