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• W2286388226 abstract "The cationic glycolipid IAXO-102, a potent TLR4 antagonist targeting both MD-2 and CD14 co-receptors, has been used as scaffold to design new potential TLR4 modulators and fluorescent labels for the TLR4 receptor complex (membrane TLR4.MD-2 dimer and CD14). The primary amino group of IAXO-102, not involved in direct interaction with MD-2 and CD14 receptors, has been exploited to covalently attach a fluorescein (molecules 1 and 2) or to link two molecules of IAXO-102 through diamine and diammonium spacers, obtaining 'dimeric' molecules 3 and 4. The structure-based rational design of compounds 1-4 was guided by the optimization of MD-2 and CD14 binding. Compounds 1 and 2 inhibited TLR4 activation, in a concentration-dependent manner, and signaling in HEK-Blue TLR4 cells. The fluorescent labeling of murine macrophages by molecule 1 was inhibited by LPS and was also abrogated when cell surface proteins were digested by trypsin, thus suggesting an interaction of fluorescent probe 1 with membrane proteins of the TLR4 receptor system." @default.
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• W2286388226 date "2016-03-11" @default.
• W2286388226 modified "2023-10-18" @default.
• W2286388226 title "Glycolipid-based TLR4 Modulators and Fluorescent Probes: Rational Design, Synthesis, and Biological Properties" @default.
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• W2286388226 doi "https://doi.org/10.1111/cbdd.12749" @default.
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