1,3,4,6-Tetra-O-acetyl-2-azido-2-deoxy-a-D-mannopyranose

1,3,4,6-O-四乙酰基-2-叠氮-2-去氧- D-甘露糖,

1,3,4,6-Tetra-O-acetyl-2-azido-2-deoxy-a-D-mannopyranose (1,3,4,6-TA) is a stable analog of the glycosidic sugar 2,6-dideoxymannose. This compound has been shown to be a potent inhibitor of the synthesis of Neisseria meningitidis capsular polysaccharides and an effective vaccine adjuvant against Mycobacterium tuberculosis. 1,3,4,6-TA is also a competitive inhibitor for the enzyme mycothiol and other thioglycosidic enzymes that are involved in the biosynthesis of mycolic acids. 1,3,4,6-TA was synthesized from 2-(N'-bromoacetamido)-2'-deoxymannose by reaction with sodium azide in acetone.

 Definition and Background

1,3,4,6-tetra-O-acetyl-2-azido-2-deoxy-alpha-D-mannopyranose (abbreviated as Ac4ManNAz) is a chemical compound widely used in chemical biology and bioorthogonal labeling techniques. It is an azide-containing sugar derivative that can selectively label biomolecules in complex biological settings. The compound's discovery can be traced back to the early 2000s when it was first synthesized by Bertozzi and co-workers (1). Since then, the compound has become a widely used tool in the field of glycobiology, enabling the detection and visualization of glycoproteins, glycolipids, and glycans in various biological systems.

Synthesis and Characterization

Several synthetic routes have been developed for the preparation of Ac4ManNAz. One of the most popular methods involves the acetylation of D-mannose with acetic anhydride, followed by azide introduction using sodium azide and triethylamine under basic conditions (2). The compound's purity can be assessed by various analytical techniques, including nuclear magnetic resonance (NMR) spectroscopy, high-performance liquid chromatography (HPLC), and mass spectrometry.

Analytical Methods

Ac4ManNAz can be detected and quantified using various analytical methods. For example, HPLC coupled with UV or fluorescence detection can be used to monitor the compound's presence and purity in reaction mixtures. NMR spectroscopy can also be used to confirm the compound's structure and assess its purity. In addition, mass spectrometry can be used for the identification and quantification of Ac4ManNAz and its derivatized products. These analytical methods are often used in combination to achieve maximum accuracy and sensitivity.

Biological Properties

Ac4ManNAz is a bioorthogonal chemical probe that can selectively label glycosylated biomolecules in living cells and animals. The compound's azide functionality allows it to react specifically and rapidly with alkyne or cyclooctyne-containing molecules in the presence of a copper (I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction or strain-promoted alkyne-azide cycloaddition (SPAAC) reaction. This bioorthogonal labeling approach enables the visualization and tracking of glycoproteins and glycans in complex biological systems, providing insights into their roles in various physiological and pathological processes.

Toxicity and Safety in Scientific Experiments

Ac4ManNAz has been extensively tested for its toxicity and safety in various scientific studies. It has been shown to have low toxicity and is not mutagenic in bacterial and mammalian cells (3). However, as with any chemical compound, proper handling and disposal protocols should be followed to ensure its safe use in research experiments.

Applications in Scientific Experiments

The unique bioorthogonal labeling property of Ac4ManNAz has made it a valuable tool in various scientific experiments. In particular, it has been widely used in glycobiology studies, including the detection and quantification of glycoproteins and glycans in cancer cells, bacteria, and viruses (4). Moreover, Ac4ManNAz has also been used to study protein trafficking, glycosylation dynamics, and host-pathogen interactions.

Current State of Research

The current state of research on Ac4ManNAz is focused on exploring its potential applications in various fields of research and industry, including biomedicine, nanotechnology, and biomaterials. For example, the compound is being investigated for its potential role in drug delivery, as well as its ability to label cells for imaging and tracking in vivo. Recent studies have also explored the use of Ac4ManNAz in the development of glycomimetics, which are compounds that mimic the structure and function of complex carbohydrates.

Potential Implications in Various Fields of Research and Industry

The potential implications of Ac4ManNAz in various fields of research and industry are vast. In biomedicine, the compound's ability to selectively label glycoproteins and glycans in living cells and animals could enable the development of novel diagnostics and therapeutics for various diseases, including cancer and infectious diseases. In nanotechnology, Ac4ManNAz could be used to functionalize nanoparticles or other materials for various applications, including biosensors, bioimaging, and drug delivery. In the biomaterials industry, the compound could be used to modify the surfaces of various materials, such as polymers or metals, for improved biomaterial performance.

Limitations and Future Directions

Despite its many applications and potentials in various research fields, Ac4ManNAz has some limitations that must be addressed in future directions. For example, the compound's reactive azide functionality can potentially interact with endogenous cellular components, leading to non-specific labeling or toxicity. Therefore, developing more specific and biocompatible azide probes that can selectively label glycosylated biomolecules in vivo remains a future direction for research. Additionally, the development of more efficient and scalable synthetic routes for Ac4ManNAz and its derivatives could enable wider applications of the compound in various research and industrial settings.

Future Directions

Possible future directions for research on Ac4ManNAz and its derivatives include:

1. Development of more specific and biocompatible azide probes that can selectively label glycosylated biomolecules in vivo.

2. Improvement of synthetic routes for Ac4ManNAz and its derivatives, to enable wider applications of the compound in various research and industrial settings.

3. Investigation of the role of Ac4ManNAz in biomaterials science, including the modification of material surfaces for improved biomaterial performance.

4. Development of novel diagnostics and therapeutics for various diseases, including cancer and infectious diseases.

5. Exploration of the potential use of Ac4ManNAz in drug delivery and in the development of glycomimetics.

6. Further investigation of the compound's toxicity and safety, as well as its effects on endogenous cellular components in vivo.

7. Development of more efficient methods for the detection and quantification of Ac4ManNAz and its derivatives in biological systems.

8. Integration of Ac4ManNAz into existing bioorthogonal labeling strategies for a better understanding of complex biological systems.

9. Investigation of the compound's effects on protein trafficking, glycosylation dynamics, and host-pathogen interactions.