TY - JOUR
T1 - Fluorescence properties of retinoid X receptor antagonist NEt-SB
AU - Yamada, Shoya
AU - Takamura, Yuta
AU - Fujihara, Michiko
AU - Kawasaki, Mayu
AU - Ito, Sohei
AU - Nakano, Shogo
AU - Kakuta, Hiroki
N1 - Funding Information:
The authors are grateful to the Division of Instrumental Analysis, Okayama University for the NMR and MS measurements. The authors are also grateful to Central Research Laboratory, Okayama University Medical School for the fluorescence measurement using a 384?well microplate (FlexStation 3).
Funding Information:
This work was partially supported by a Grant-in-Aid from the Japan Society for the Promotion of Science (JSPS) 12J06716 (to S.Y.), 18K14391 (to S.N.), 20J23771 (to M.K.) and by grants from Okayama Foundation for Science and Technology (to H.K.), The Tokyo Biochemical Research Foundation (TBRF) (to H.K.), Kobayashi Foundation (to H.K.), Kobayashi Foundation (to H.K.), and scholarship support from the Shoshisha Foundation (to Y.T.).
Publisher Copyright:
© 2020 Elsevier Ltd
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/1/1
Y1 - 2021/1/1
N2 - 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.
AB - 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.
KW - Binding assay
KW - Fluorescence
KW - RXR
KW - Solvatochromism
KW - Stilbene
UR - http://www.scopus.com/inward/record.url?scp=85095936744&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85095936744&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2020.127666
DO - 10.1016/j.bmcl.2020.127666
M3 - Article
C2 - 33152377
AN - SCOPUS:85095936744
SN - 0960-894X
VL - 31
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
M1 - 127666
ER -