GlcNAc-PP-dolichol Inhibitor Development Service at CD BioGlyco

The first step in N-glycan synthesis is the transfer of UDP-N-acetylglucosamine (UDP-GlcNAc) to polyol phosphate (Dol-P) via N-acetylglucosamine phosphotransferase (GlcNAc-1-P-transferase or GPT), thereby generating polyol hydroxypyrophosphate N-acetylglucosamine (Dol-PP-GlcNAc). GPT is a key enzyme involved in this process, its function loss mutation or overexpression cause a variety of diseases. Based on this mechanism, CD BioGlyco provides a high-quality GlcNAc-PP-dolichol inhibitor development service.

• GlcNAc-PP-dolichol inhibitor production service

Tunicamycin is a common GlcNAc-PP-dolichol inhibitor, which is a natural product produced by the fungus Streptomyces lysosuperificus and prevents glycoprotein modification by interfering with the GlcNAc-PP-dolichol synthesis process. CD BioGlyco provides mature tunicamycin production service through efficient technical means.

• Bacteria culture

CD BioGlyco selects strains containing S. lysosuperificus and promotes the growth of the strain and the accumulation of metabolites by optimizing the growth conditions of the culture medium.

• Fermentation

CD BioGlyco transfers the selected strains to the fermenter and provides appropriate culture conditions, including temperature, pH, oxygen supply, etc. By controlling these conditions, tunicamycin production is optimized.

• Extraction and purification

After the fermentation process is completed, we collect the fermentation broth or bacterial cells and perform extraction to isolate the target product. Various purification techniques such as chromatography, crystallization, etc. are then used to purify tunicamycin.

• Structure confirmation

CD BioGlyco conducts structural identification of extracted and purified tunicamycin products using analytical techniques (such as mass spectrometry, nuclear magnetic resonance, etc.) to ensure that they meet the prescribed standards.

• GlcNAc-PP-dolichol inhibitor development service

CD BioGlyco develops more effective and selective GlcNAc-PP-dolichol inhibitors through chemical synthesis methods. Deoxynojirimycin and its derivatives are a class of compounds with GlcNAc-PP-dolichol inhibitory activity. As enzyme inhibitors, they interfere with the activity of specific enzymes, thereby affecting the synthesis or transport of GlcNAc-PP-dolichol. In addition, we provide inhibitory activity evaluation for synthetic GlcNAc-PP-dolichol inhibitors through a series of in vitro experiments and analytical techniques to determine their potency and selectivity.

Fig.1 GlcNAc-PP-dolichol inhibitor development service. (CD BioGlyco)

Publication

Technology: Bioluminescence imaging

Journal: Clinical Cancer Research

IF: 13.801

Published: 2010

Results: The authors used bioluminescence imaging to monitor the in vitro and in vivo dynamics of N-linked glycosylation (NLG) through imaging studies to determine the effective dose of the GlcNAc-1-phosphotransferase inhibitor tunicamycin. The authors performed daily imaging of mice after injecting a single dose of 0.75 mg/kg tunicamycin. The results showed that NLG inhibition in vivo lasted for several days, with a peak luminescence occurring 48 to 72 hours after injection. While control-treated animals did not show enhanced luminescence over time.

Fig.2 Tunicamycin-induced imaging studies in mice. (Contessa, et al., 2010)

Applications

• Studying glycoprotein modifications: By inhibiting the synthesis or transport of GlcNAc-PP-dolichol, which explores the regulatory mechanisms, signaling pathways, and effects related to cell functions and disease of glycoprotein modifications.
• Drug screening: The development of GlcNAc-PP-dolichol inhibitors is applied in drug screening platforms to evaluate the impact of candidate compounds on glycoprotein modifications, which helps discover new therapeutic targets and drugs, especially in diseases involving abnormal modifications of glycoproteins.
• Disease model establishment and validation: Some tumor diseases are associated with glycoprotein modification disorders. By using GlcNAc-PP-dolichol inhibitors, it is possible to model the characteristics of these diseases and evaluate their potential role in disease pathogenesis.

Advantages

• Diversified solutions: CD BioGlyco provides diversified Inhibitor Development Solutions according to client needs, including synthesis, screening, optimization, and evaluation.
• Drug screening means: CD BioGlyco has established a massive high-throughput drug screening means to evaluate the inhibitory activity and selectivity of candidate GlcNAc-PP-dolichol inhibitors, thereby accelerating the drug discovery process.
• Animal model verification: CD BioGlyco provides validation for the efficacy and safety of GlcNAc-PP-dolichol inhibitors in specific disease models, providing strong data support for preclinical research.

CD BioGlyco has an efficient, multidisciplinary R&D team that works collaboratively to quickly deliver high-quality GlcNAc-PP-dolichol inhibitor development results. Please feel free to contact us if you are interested in our services and we are your best partner.