Fluorescence properties of retinoid X receptor antagonist NEt-SB. (1st January 2021)

• Record Type: Journal Article
• Authors: Yamada, Shoya; Takamura, Yuta; Fujihara, Michiko; Kawasaki, Mayu; Ito, Sohei; Nakano, Shogo; Kakuta, Hiroki
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 31(2021)
• Publication Date: 2021-01-01
• Subjects: Abs absorption -- CTCL cutaneous T-cell lymphoma -- Em emission -- Ex excitation -- Fl fluorescence -- LBD ligand-binding domain -- LXR liver X receptor -- PPAR peroxisome proliferator-activated receptor -- RAR retinoic acid receptor -- hRXR human retinoid X receptor -- SD standard deviation -- TR thyroid hormone receptor -- Trp tryptophan -- VDR vitamin D receptor; RXR -- Fluorescence -- Stilbene -- Solvatochromism -- Binding assay; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2020.127666
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Ligands of retinoid X receptors (RXRs) are effective against various diseases, so there is a need for efficient screening methods to discover new ligands. Existing screening methods are complex and time-consuming, and a simple fluorescence assay would be highly desirable. Here, we focused on NEt-SB (4 ), which has a stilbene structure, as a candidate for this purpose, and examined its fluorescence properties in detail. The fluorescence intensity of 4 was remarkably increased in highly viscous solvents and upon binding to hRXRα-LBD, due to suppression of free rotation of the stilbene moiety. Although the relatively low fluorescence intensity and the short fluorescence wavelength of 4 make this compound itself unsuitable for use in RXR binding assay, our findings provide a basis for further structural evolution, which may lead to a derivative that would be suitable for fluorescence assay of RXR binders.