A bifunctional imidazolium-based cholesterol analog for the tracking of cellular cholesterol distributions and cholesterol–protein interactions

Abstract

Cholesterol is a sterol lipid found in all higher eukaryotic organisms. It is required to consolidate the basic structural integrity and dynamic principles of cellular membranes and participates in many...

Combining lipid-mimicking-enabled transition metal and enzyme-mediated catalysis at the cell surface of E. coli

“…Consequently, the Pd loading seems to be reliant on the cholesterol backbone, thereby corroborating the assumption that the CHIM backbone leads to bacterial membrane integration. Presuming that CHIM–Pd would indeed be embedded into the cell membrane with its headgroup oriented to the cell surface as previously reported for other CHIMs, 9,10 this should enable Pd-mediated reactions in the exterior of CHIM–Pd-treated cells. A commonly applied reaction using palladium salts or complexes in biological systems is the depropargylation of propargyl ethers.…”

“…In this context, the attachment of a clickable azide linker enabled the functionalization of membrane surfaces either via membrane incorporation of pre-clicked derivatives or via on-membrane surface click chemistry. 9,10…”

“…This combination could allow for the spatial release of a labeling compound or prodrug in the vicinity of the addressed site. Additionally, given the already reported successful application of CHIM derivatives in membrane vesicles as well as in mammalian cell membranes, 9,10 the use of CHIM-based metal catalysts might not be limited to bacterial membrane functionalization but can also potentially be extended to other types of (cellular) membranes. However, here initial experiments in mammalian cells showed that careful catalyst tuning and reaction optimization depending on the investigated cell type might be crucial to obtain compatible and efficient catalyst systems.…”

“…8 In particular, a clickable imidazolium-based cholesterol analog was developed that has been shown to readily integrate into the plasma membrane of mammalian cell lines, where it could be employed for membrane surface functionalization with a fluorescent dye. 9,10 However, more commonly imidazolium salts serve as precursors to form N -heterocyclic carbenes (NHCs) that are employed as electron-rich ligands to tune properties and reactivity of transition metal complexes/catalysts in organic synthesis. 11 (NHC-)transition metal complexes have, however, also been reported to enable classic synthetic organic reactions in biological environments.…”