Synthetic probes and chemical tools in sphingolipid research

Metabolic Labeling-Based Chemoproteomics Establishes Choline Metabolites as Protein Function Modulators

“…In summary, our studies have provided novel insights on choline lipid biology and established the importance of choline metabolite–protein interactions in protein function. Our metabolic labeling studies demonstrate that the mammalian choline lipid biosynthetic machinery is remarkably promiscuous, and our choline probes add to the rapidly expanding toolkit of lipidic metabolic labeling probes that include those for labeling both the hydrophobic tails ,− and headgroups of lipids, sphingolipids, − inositol lipids, and phosphatidic acid . Moreover, our discovery that choline lipid headgroups are susceptible to chemical remodeling via sequential dealkylation and methylation in mammalian cells will engender studies focused on elucidating the biochemical basis of this mechanism and its role in lipid homeostasis and disease pathophysiology.…”

Fluorogenic Reactions in Chemical Biology: Seeing Chemistry in Cells

“…Because of these advantages, fluorogenic reactions are ideal reactions for chemical biology applications. Additionally, after the fluorogenic reaction, a very strong fluorescence signal can be obtained; the starting materials do not need to be fluorescent or weakly fluorescent, which is of particular interest for in vivo labeling in bioconjugation, such as labeling and sequencing of nuclear acids − and labeling of proteins, lipids, − glycans, and others . In addition, enzyme-triggered bioorthogonal cleavage fluorogenic reactions have attracted wide attention because of their high biocompatibility, fast reaction rate, and robustness. − These fluorogenic reactions can also be applied in detecting and acting as no-washing probes for fluorescent imaging. , …”

“…On the basis of the importance of sphingolipids in biology, many ways to label sphingolipids and metabolites have been reported and reviewed. 111 In 2020, Devaraj et al 140 first reported a fluorogenic probe for the detection of the significant signaling lipid sphingosine in cultured mammalian cells (Figure 24e). The strategy has shown a promising outlook for the diagnosis of lipid storage disorders.…”

In situ synthesis of artificial lipids

“…It is worth mentioning that there are up to 26 different enzymes that regulate ceramide levels [48]. Additionally, such class of lipids have low membrane permeability [49]. All these factors make ceramides challenging to study in cells.…”