A novel fluorescence competition assay for retinoic acid binding proteins

Tomlinson, Charles W.E.; Chisholm, David R.; Valentine, Roy; Whiting, Andrew; Pohl, Ehmke

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 non-labeled 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.

Citation

Tomlinson, C. W., Chisholm, D. R., Valentine, R., Whiting, A., & Pohl, E. (2018). A novel fluorescence competition assay for retinoic acid binding proteins. ACS Medicinal Chemistry Letters, 9(12), 1297–1300-1300. https://doi.org/10.1021/acsmedchemlett.8b00420

• Journal Article Type: Article
• Acceptance Date: Nov 9, 2018
• Online Publication Date: Nov 9, 2018
• Publication Date: Dec 31, 2018
• Deposit Date: Nov 13, 2018
• Publicly Available Date: Nov 9, 2019
• Journal: ACS Medicinal Chemistry Letters
• Print ISSN: 1948-5875
• Electronic ISSN: 1948-5875
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 9
• Issue: 12
• Pages: 1297–1300-1300
• DOI: https://doi.org/10.1021/acsmedchemlett.8b00420