727977-97-1—Key sugar nucleotides for glycosylation engineering and drug development

UDP-4-fluoro-4-deoxy-D-galactosaminedisodium salt (UDP-4-fluoro-4-deoxy-D-acetylgalactosaminedisodium salt) is a sugar nucleotide that has been specifically fluorinated. As an important tool molecule in glycobiology and glycosylation engineering research, it provides a unique chemical and functional basis for accurately regulating the glycosylation process and developing new carbohydrate therapies by simulating the structure of natural sugar donors and introducing fluorine atoms.

Chemical Information

Chemical name: UDP-4-fluoro-4-deoxy-D-acetylgalactosamine disodium salt

Common name: UDP-4FGalNAc disodium salt

Chemical formula: C17H27FN3NaO16P2

Molecular weight: 633.34 g/mol

CAS number: 727977-97-1

Category: Sugar Nucleotides

Structural features

This compound has been precisely fluorinated based on the structure of the classic sugar nucleotide UDP-GalNAc. Its core features include:

Key fluorine atom substitution: On the 4th carbon atom of the galactosamine sugar ring, the original hydroxyl group (OH) is replaced by a fluorine atom (F). This modification spatially simulates a hydroxyl group, but its strong electronegativity and different bonding characteristics can significantly change the electron distribution, conformational stability and interaction with enzymes of the sugar ring.

Stable sugar nucleotide backbone: retains uridine diphosphate (UDP) as a high-energy carrier to provide energy drive for glycosyl transfer reactions. Its disodium salt form improves water solubility and storage stability.

Metabolic resistance design: The introduction of the fluorine atom at position 4 can make the sugar analog resist degradation by certain glycosidase enzymes or metabolic pathways and extend its action time in biological systems. It is a common strategy for designing mechanistic inhibitors or stable substrate analogs.

Main applications and advantages

Glycosyltransferase research and inhibitor development

As a sugar donor analog with a unique structure, it is often used to study the catalytic mechanism, substrate specificity and active site structure of glycosyltransferases (especially those enzymes that use UDP-GalNAc as a substrate, such as certain polypeptide N-acetylgalactosamine transferases). Its fluorine atoms can serve as probes to study key hydrogen-bonding interactions between enzymes and substrates. In addition, it itself or the molecules synthesized using it as a template are often used as competitive inhibitors or transition state analogs to regulate abnormal glycosylation processes.

Glycoprotein and glycolipid synthesis and engineering

When synthesizing glycoconjugates (glycoproteins, glycolipids) in vitro or through chemoenzymatic methods, it can be used as a non-natural glycosyl donor to introduce fluorinated GalNAc residues into specific oligosaccharide chains or target molecules. This provides the possibility to prepare fluorine-labeled glycoconjugates with clear structures and special physicochemical or biological activities for functional research, imaging probe development, or construction of new biological agents.

Disease mechanism research and drug discovery

Abnormal glycosylation is closely related to various diseases such as cancer, inflammation, and congenital glycosylation disorders. This fluorinated sugar nucleotide can be used to competitively interfere with specific GalNAc glycosylation pathways in cells or model systems, helping to reveal the specific functions of specific glycoforms in the occurrence and development of diseases. Inhibitors designed based on their structure are expected to become potential lead compounds for the treatment of diseases that rely on specific glycosyltransferase activity, such as certain tumors.

Tool molecules and diagnostic applications

can be used as a standard or probe substrate to develop analytical methods for detecting glycosyltransferase activity. The unique fluorinated sugar chain structure that may be produced or integrated during the metabolic process has the potential to be used as a metabolic marker or a tool for tracking sugar fate, or as a reference molecule for biomarker research in certain enzyme deficiency diseases.

Conclusion

UDP-4-fluoro-4-deoxy-D-acetylgalactosamine disodium salt represents an example of a rationally designed tool molecule in glycoscience. By combining the precision of fluorine chemistry with the complexity of glycobiology, it not only deepens people's understanding of glycosylation, a key life process, but also provides irreplaceable molecular intervention and construction capabilities in the broad chain from basic enzymology research to innovative drug development. As glycoscience becomes increasingly prominent in the therapeutic landscape, the value of these carefully engineered sugar nucleotides will continue to grow.

The above information is provided by the editor of KASONS and is for scientific research only.