Metabolic glycan labeling has emerged as a central tool for glycan imaging and glycoproteomic profiling in live cells.  Unnatural sugars containing a bioorthogonal functional group (e.g., the azdie) are uptaken by the cells, enter the glycan biosynthetic pathways, and metabolically incorporated into cellular glycans.  With the azide incorporated into the glycans, bioorthogonal reactions (e.g., click chemistry) are used to install imaging probes for imaging or affinity tags for enrichment and proteomic profiling.  As a common practice to enhance cellular uptake, the azidosugars are usually per-O-acetylated to improve their hydrophobicity and membrane penetration. <br/><br/>We recently discovered that the peracetyalted monosaccharides inside the cells can directly react with cysteines in a non-enzymatic manner, which may compromise the specificity and validity of metabolic glycan labeling.  Detailed mechanistic investigation unveils an atypical glycosylation termed protein S-glyco-modification, which produces 3-thiolated sugars in the hemiacetal form, rather than typical glycosides. Notably, this artificial S-glyco-modification has been overlooked in the filed for more than two decades.  To solve this issue, we have now developed the next-generation unnatural monosaccharides that have both high labeling efficiency and no artificial S-glyco-modification for metabolic glycan labeling.

S-glyco-modification: one thing you should know about metabolic glycan labeling

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.