N-Azidoacetylmannosamine-tetraacylated
[CAS# 361154-30-5]

Identification

• Classification: Inorganic chemical industry >> Inorganic salt >> Hydride, nitride, azide >> Azide
• Name: N-Azidoacetylmannosamine-tetraacylated
• Synonyms: ManNaz; Ac4ManNAz; [(2R,3S,4R,5S)-3,4,6-triacetyloxy-5-[(2-azidoacetyl)amino]oxan-2-yl]methyl acetate
• Molecular Formula: C₁₆H₂₂N₄O₁₀
• Molecular Weight: 430.37
• CAS Registry Number: 361154-30-5
• SMILES: CC(=O)OC[C@@H]1[C@H]([C@@H]([C@@H](C(O1)OC(=O)C)NC(=O)CN=[N+]=[N-])OC(=O)C)OC(=O)C

Safety Data

• Hazard Symbols: GHS02;GHS07 Danger
• Hazard Statements: H228-H315-H319
• Precautionary Statements: P240-P210-P241-P264-P280-P302+P352-P370+P378-P337+P313-P305+P351+P338-P362+P364-P332+P313
• Transport Information: UN 1325

Discovory and Applicatios

N-Azidoacetylmannosamine-tetraacylated is a synthetic derivative of N-acetylmannosamine (ManNAc), a monosaccharide commonly involved in the biosynthesis of sialic acids in mammalian cells. This modified compound contains an azide group replacing the acetyl group at the nitrogen position and includes four acyl (typically short-chain fatty acid) groups that increase membrane permeability. It is chemically described as peracetylated N-azidoacetylmannosamine and is often referred to in the literature as Ac₄ManNAz.

The discovery and development of N-azidoacetylmannosamine-tetraacylated emerged from research in the late 1990s and early 2000s focused on metabolic glycoengineering. This field aimed to exploit the biosynthetic pathways of glycans to introduce chemical groups not naturally found in cells. The azide group was selected for its small size and bioorthogonal reactivity—meaning it does not interfere with native biochemical processes—making it suitable for specific chemical labeling reactions such as the Staudinger ligation or copper-catalyzed azide-alkyne cycloaddition (CuAAC), commonly known as "click chemistry."

To introduce the azide functionality into cellular glycans, researchers developed derivatives like Ac₄ManNAz, which can passively diffuse across cell membranes due to the presence of acetyl groups. Once inside the cell, intracellular esterases remove the acetyl groups, freeing the sugar for metabolism. The deacetylated N-azidoacetylmannosamine is processed through the sialic acid biosynthetic pathway and incorporated into sialoglycoconjugates, especially glycoproteins and glycolipids. The resulting azide-functionalized sialic acids appear on the cell surface, enabling bioorthogonal labeling.

This strategy was notably applied in studies of cell-surface glycans, allowing scientists to tag and visualize glycoproteins in live cells with high specificity. By reacting the azide moieties with fluorescent alkyne-containing probes, researchers could monitor dynamic glycosylation events in real time. This technique has been used to study a range of biological phenomena, including cell signaling, cancer progression, and immune cell interactions.

The compound is also used in targeted drug delivery and imaging. By introducing azide-labeled glycans onto specific cell populations, therapeutics or contrast agents conjugated to complementary alkyne groups can be selectively delivered or visualized. In particular, this approach has been explored in the context of cancer, where aberrant glycosylation patterns provide a selective target for tumor imaging or therapy.

In addition to its use in mammalian cell systems, N-azidoacetylmannosamine-tetraacylated has been employed in microbial and stem cell studies. It serves as a general tool for probing glycan structures and dynamics across various biological systems. Its compatibility with non-toxic labeling conditions has made it valuable in in vivo imaging and metabolic tracking studies.

The synthesis of N-azidoacetylmannosamine-tetraacylated involves multiple steps, typically starting from ManNAc. The hydroxyl groups are acylated, and the acetamido group is replaced with an azidoacetamido moiety. This modification retains the ability to be processed by the native biosynthetic enzymes, ensuring metabolic incorporation into sialylated structures.

N-azidoacetylmannosamine-tetraacylated is thus a widely used reagent in chemical biology, enabling selective and non-invasive labeling of glycoproteins and other glycoconjugates in living systems. Its development marked a key advancement in the study of glycosylation and remains central to metabolic labeling techniques in modern research.

References

2017. Physiological Effects of Ac4ManNAz and Optimization of Metabolic Labeling for Cell Tracking. Theranostics, 7(5).
DOI: 10.7150/thno.17711

2017. Selective In Vivo Metabolic Cell Labeling Mediated Cancer Targeting. Nature Chemical Biology, 13(4).
DOI: 10.1038/nchembio.2297

2019. Exploiting metabolic glycoengineering to advance healthcare. Nature Reviews Chemistry, 3(9).
DOI: 10.1038/s41570-019-0126-y