Synthesis and biological evaluation of cationic TopFluor cholesterol analogues

0554712 - ÚMG 2022 RIV US eng J - Journal Article
Jurasek, M. - Valečka, Jan - Novotný, Ivan - Kejik, Z. - Fahnrich, J. - Marešová, A. - Tauchen, J. - Bartůněk, Petr - Dolenský, B. - Jakubek, M. - Drasar, P. - Králová, Jarmila
Synthesis and biological evaluation of cationic TopFluor cholesterol analogues.
Bioorganic Chemistry. Roč. 117, December (2021), č. článku 105410. ISSN 0045-2068. E-ISSN 1090-2120
R&D Projects: GA ČR GA17-02836S; GA MŠMT(CZ) LM2018130; GA MŠMT(CZ) EF16_013/0001775
Research Infrastructure: CZ-OPENSCREEN III - 90130
Institutional support: RVO:68378050
Keywords : TopFluor cholesterol analogues * Sterol * Cholesterol transport * Fluorescence imaging * Trafficking disorders
OECD category: Biochemistry and molecular biology
Impact factor: 5.307, year: 2021
Method of publishing: Limited access
https://www-sciencedirect-com.d360prx.biomed.cas.cz/science/article/pii/S0045206821007872?via%3Dihub

Cholesterol is not only a major component of the cell membrane, but also plays an important role in a wide range of biological processes and pathologies. It is therefore crucial to develop appropriate tools for visualizing intracellular cholesterol transport. Here, we describe new cationic analogues of BODIPY-Cholesterol (TopFluorCholesterol, TF-Chol), which combine a positive charge on the sterol side chain and a BODIPY group connected via a C-4 linker. In contrast to TF-Chol, the new analogues TF-1 and TF-3 possessing acetyl groups on the A ring (C-3 position on steroid) internalized much faster and displayed slightly different levels of intracellular localization. Their applicability for cholesterol monitoring was indicated by the fact that they strongly label compartments with accumulated cholesterol in cells carrying a mutation of the Niemann-Pick disease-associated cholesterol transporter, NPC1.
Permanent Link: http://hdl.handle.net/11104/0329377