Exploring the Binding Proteins of Glycolipids with Bifunctional Chemical Probes

Glycolipids are important structural components of biological membranes and perform crucial functions in living systems, including signaling transduction and interaction with extracellular environment. However, the mechanistic exploration of glycolipids in vivo is challenging because they are not genetically encoded. Herein, we designed and synthesized a series of bifunctional monogalactosyldiacylglycerol (MGDG) probes as a model by introducing diazirine and terminal alkyne moieties on an aliphatic chain. In combination with proteome profiling and molecular modeling, we have demonstrated that MGDG alleviates inflammation by antagonizing TLR4.