New 20-hydroxycholesterol-like compounds with fluorescent NBD or alkyne labels: Synthesis, in silico interactions with proteins and uptake by yeast cells
| Autor: | L.A. Novikova, Nikolai N. Sluchanko, Mikhail A. Rubtsov, N. S. Frolova, Y. V. Faletrov, Vladimir M. Shkumatov, Kristina V. Tugaeva, Matvey S. Horetski, Isaeva Lv, Vera S. Efimova, Quingquing Lin |
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| Rok vydání: | 2020 |
| Předmět: |
Receptors
Steroid Saccharomyces cerevisiae Proteins Membrane permeability Oxysterol In silico 030303 biophysics Saccharomyces cerevisiae Biochemistry 03 medical and health sciences polycyclic compounds Humans Molecular Biology Benzofurans Liver X Receptors 030304 developmental biology 0303 health sciences Binding Sites biology Chemistry Organic Chemistry Membrane Proteins Yarrowia Cell Biology Metabolism biology.organism_classification Hydroxycholesterols Yeast Molecular Docking Simulation Microscopy Fluorescence Docking (molecular) Alkynes Pregnenolone lipids (amino acids peptides and proteins) Protein Binding |
| Zdroj: | Chemistry and Physics of Lipids. 227:104850 |
| ISSN: | 0009-3084 |
| DOI: | 10.1016/j.chemphyslip.2019.104850 |
| Popis: | 20-hydroxycholesterol is a signaling oxysterol with immunomodulating functions and, thus, structural analogues with reporter capabilities could be useful for studying and modulating the cellular processes concerned. We have synthesized three new 20-hydroxycholesterol-like pregn-5-en-3β-ol derivatives with fluorescent 7-nitrobenzofurazan (NBD) or Raman-sensitive alkyne labels in their side-chains. In silico computations demonstrated the compounds possess good membrane permeability and can bind within active sites of known 20-hydroxycholesterol targets (e.g. Smoothened and yeast Osh4) and some other sterol-binding proteins (human LXRβ and STARD1; yeast START-kins Lam4S2 and Lam2S2). Having found good predicted membrane permeability and binding to some yeast proteins, we tested the compounds on microorganisms. Fluorescent microscopy indicated the uptake of the steroids by both Saccharomyces cerevisiae and Yarrowia lipolytica, whereas only S. cerevisiae demonstrated conversion of the compounds into 3-O-acetates, likely because 3-O-acetyltransferase Atf2p is present only in its genome. The new compounds provide new options to study the uptake, intracellular distribution and metabolism of sterols in yeast cells as well as might be used as ligands for sterol-binding proteins. |
| Databáze: | OpenAIRE |
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