Azide-labeled surface glycoconjugates on neural progenitor cells

Azide-labeled surface glycoconjugates on neural progenitor cells (NPCs) are synthetic chemical handles created through metabolic glycan labeling, a technique where cells incorporate non-natural sugars into their surface glycoproteins and glycolipids [1]. By treating NPCs with precursors like tetraacetylated N-azidoacetylmannosamine (Ac4ManNAz), the cell's biosynthetic machinery displays azide groups on the plasma membrane, which are absent in native biological systems [2]. These azides serve as highly specific targets for bioorthogonal click chemistry, specifically the strain-promoted azide-alkyne cycloaddition (SPAAC), allowing for the covalent attachment of drugs, imaging agents, or nanoparticles modified with strained alkynes like dibenzocyclooctyne (DBCO) [3]. This approach is primarily used in regenerative medicine to track the migration of transplanted NPCs or to deliver therapeutic payloads directly to these cells to enhance their survival or differentiation in neurodegenerative disease models [4]. While providing exceptional targeting precision, the strategy is limited by the potential metabolic toxicity of the sugar precursors and the natural turnover of the cell surface, which leads to the gradual loss of the azide label over time [5]. [1] Laughlin, S. T., & Bertozzi, C. R. (2009). Metabolic labeling of glycans with azido sugars and subsequent glycan-profiling and visualization via Staudinger ligation. Nature Protocols. [2] Lee, S., et al. (2016). Metabolic labeling of neural stem cells with azide-modified sugars for bioorthogonal imaging. Bioconjugate Chemistry. [3] Agard, N. J., et al. (2004). A strain-promoted [3 + 2] azide-alkyne cycloaddition for covalent modification of biomolecules in living systems. JACS. [4] Wang, H., et al. (2017). Bioorthogonal click chemistry for targeted drug delivery. Angewandte Chemie. [5] Chang, P. V., et al. (2010). Copper-free click chemistry in living animals. PNAS.

Other names

Azide-modified glycansMetabolically labeled NPC glycoconjugatesNPC-AzAzido-labeled cell surface glycans

Strain-promoted azide-alkyne cycloaddition (SPAAC) involving bioorthogonal click chemistry between surface azides and strained alkyne-functionalized molecules.