Ac4GalNAz: A core chemical tool for metabolic labeling and glycosylation studies 653600-56-7
1,3,4,6-Tetra-oxo-acetyl-2-[(azidoacetyl)amino]-2-deoxy-β-D-galactopyranose, often referred to as N-azidoacetylgalactosamine tetraester (Ac4GalNAz), is an indispensable modified sugar molecule in the fields of glycobiology and chemical biology. As a key reagent for metabolic glycoengineering, it enables researchers to analyze, track and engineer glycosylation modifications that are crucial in life processes with unprecedented precision and flexibility.
1,3,4,6-Tetra-oxo-acetyl-2-[(azidoacetyl)amino]-2-deoxy-β-D-galactopyranose, often referred to as N-azidoacetylgalactosamine tetraester (Ac4GalNAz), is an indispensable modified sugar molecule in the fields of glycobiology and chemical biology. As a key reagent for metabolic glycoengineering, it enables researchers to analyze, track and engineer glycosylation modifications that are crucial in life processes with unprecedented precision and flexibility.
Chemical Information
Chemical name: 1,3,4,6-Tetra-oxo-acetyl-2-[(azidoacetyl)amino]-2-deoxy-β-D-galactopyranose
Common name: N-azidoacetylgalactosamine tetraester (Ac4GalNAz)
Chemical formula: C16H22N4O10
Molecular weight: 430.37 g/mol
CAS number: 653600-56-7
Category: Metabolic Probe Reagents
Structural features
The exquisite design of Ac4GalNAz integrates two key chemical modifications that make it superior to natural sugar molecules:
• Azide-labeled handle: The azidoacetamido moiety of the molecule introduces a chemically inert but highly reactive azide group (-N3) at the 2-position of the sugar moiety. This group can be efficiently and specifically covalently linked to probes or functional molecules containing alkyne groups through copper-catalyzed or strain-promoted alkyne-azide cycloaddition reactions, acting as a "chemical handle."
• Acetyl ester protecting groups enhance delivery: Four acetyl groups fully protect the hydroxyl group, forming a lipophilic precursor. This modification significantly enhances the cell membrane permeability of the molecule, allowing it to enter cells efficiently. Subsequently, intracellular non-specific esterases hydrolytically remove the acetyl group, releasing the biologically active monosaccharide substrate GalNAz, which can be utilized by the cell's own glycosylation pathway.
Main applications and advantages
Visualization and dynamic analysis of cell surface glycosylation
As an azide analog of the natural sugar molecule N-acetylgalactosamine (GalNAc), Ac4GalNAz can be taken up by cells and metabolically integrated into mucin-type O-linked sugar chains. The spatiotemporal specific labeling, imaging, isolation and identification of specific glycoproteins or global glycosylation repertoires can be achieved through subsequent click chemistry reactions with alkyne probes bearing fluorophores, biotin or enrichment tags. This technology provides a powerful tool for studying glycosylation changes during cancer development, immune recognition, intercellular communication and other processes.
Site-directed functionalization and drug conjugation of glycoproteins
Taking advantage of the specificity of its azide tag, Ac4GalNAz metabolically labeled glycoproteins can achieve site-selective functional expansion. Researchers can precisely couple antibodies, toxins, enzymes or nanocarriers to specific sugar chain sites on target glycoproteins through bioorthogonal chemistry. This approach opens up new avenues for the development of novel antibody-drug conjugates, cell surface engineering, and the construction of synthetic glycoprotein materials with specific functions.
Exploration and regulation of sugar biosynthetic pathways
By tracking the metabolic fate of Ac4GalNAz and its integrated products in cells, we can deeply explore the activity, substrate specificity and pathway regulation mechanisms of O-glycosylation and other related glycosyltransferases. It is also a powerful probe for studying diseases related to abnormal glycosylation, such as congenital disorders of glycosylation, and can be used to screen potential small molecule modulators that affect the glycosylation process.
Conclusion
Ac4GalNAz cleverly integrates the biocompatibility of metabolic substrates with the efficient reactivity of bioorthogonal chemical groups, bridging complex biological systems and precise chemical manipulation. From the interpretation of the sugar code in basic science to the design and construction of new glycoprotein drugs in biotechnology, this molecule continues to promote the cutting-edge development of sugar science and is an indispensable chemical light source for exploring the "dark matter" field of glycosylation of life.
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