GlycoCLICK™-based Glycosidase Inhibitor Development Service
Unlocking the Potential of GlycoCLICK™-based Glycosidase Inhibitor
Glycosidase inhibitors prevent glycosidases from catalyzing the breakdown of substrates by binding to the substrate and interfering with its active function, either through competitive inhibition or non-competitive inhibition. CD BioGlyco provides a wide range of glycosidase inhibitor development services using click chemistry, as well as inhibitory capacity assays. We provide high-quality GlycoCLICK™-based Enzyme Inhibitor and Carbohydrate Click-based Lectin Ligand Development services. CD BioGlyco provides various GlycoCLICK™-based Drug Development services such as Protein Tyrosine Phosphatase (PTP) Inhibitor Development and O-GlcNAcase Inhibitor Development.
- Glycosidase Inhibitor Synthesis via Click Chemistry
CD BioGlyco uses the popular click-azide-alkyne coupling to connect a large number of natural and unnatural patterns. Our lab prepares a variety of triazolyl glycoconjugates, alkylated alkyne-containing or azido-based derivatives, and then performs copper-catalyzed azide-alkyne cycloaddition. Notably, we fine-tune the reaction parameters to improve the product yield and inhibition capacity.
- Glycosidase Inhibitor Modification
To improve the glycosidase inhibitory ability and specificity of GlycoCLICK™-based glycosidase inhibitor, we provide structural modification services as follows:
- Alterations in the configuration and number of the hydroxyl groups in the pyridine ring
- Adjust the length of the interval
- Altering the hydrophobicity of the imino junction part
- Modified substitution patterns for the stereochemistry and imino sugar moieties
- Glycosidase Inhibitor Biological Evaluation
- Characterization: For the synthesized derivatives, we provide 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, thin layer chromatography (TLC), and electrospray ionization mass spectrometry (ESI-MS) analysis.
- Inhibiting capacity assay: Our lab provides professional analysis services including cell culture and assay, disease mouse model construction, observation, and analysis services.
Fig.1 Schematic diagram of GlycoCLICK™-based glycosidase inhibitor development service. (CD BioGlyco)
Publication
Technology: Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction, NMR spectroscopy, ESI-MS
Journal: Pharmaceuticals
Published: 2020
IF: 5.215
Results: In this work, researchers have synthesized a series of multivalent clusters of deoxynojirimycin via CuAAC using two alkyne-assembled calix[8]arene scaffolds, an 8-valent [8]aryl core, and a 6-valent 1,5-diene bridging scaffold. The researchers identified and characterized each intermediate by ESI-MS and NMR. Then, the inhibitory capacity was assessed with the aid of the glycosidase Jack Bean α-mannosidase (JBα-man) found that changes in the multivalent effect were correlated with the ring size, the internal localized density or the possible role of the aromatic nucleus. In addition, the assay revealed that all clusters with C9 alkyl chains showed a favorable multivalent effect.
Fig.2 Two-dimensional nuclear magnetic resonance spectroscopy of compound. (Schneider, et al., 2020)
Applications
- GlycoCLICK™-based glycosidase inhibitors lower blood glucose by delaying the absorption of carbohydrates with a good safety profile. It provides references for the development and utilization of glycosidase inhibitors in the field of diabetes.
- GlycoCLICK™-based glycosidase inhibitors are novel biological targets for drug development and utilization, which are also targeted in diseases such as viral infections, lysosomal storage disorders, and tumor metastasis.
- In the study of bacterial infections, glycosidase inhibitors block bacterial cell wall synthesis, thereby inhibiting bacterial growth.
Frequently Asked Questions
- How do glycosidase inhibitors interfere with the catalytic activity of enzymes?
Glycosidase inhibitors bind to glycosidases and interfere with their active functions, thereby preventing glycosidases from catalyzing the breakdown of substrates. Glycosidase inhibitors inhibit the activity of enzymes mainly through the following two mechanisms:
- Competitive inhibition: Glycosidase inhibitors compete with glycosidases for substrate binding sites, reducing the probability of substrate binding to the enzyme and thus inhibiting the catalytic activity of the enzyme.
- Noncompetitive inhibition: Glycosidase inhibitors bind to the non-substrate binding site, changing the conformation of the enzyme and compromising its ability to catalyze the catalytic substrate.
- What are the advantages of glycosidase inhibitors?
- The mechanism of action of glycosidase inhibitors allows them to block the breakdown and metabolism of glycoside compounds, thus leading to the accumulation of these compounds in the body. This has potential benefits for the treatment of certain diseases such as bacterial infections.
- The inhibition of digestive enzymes by glycosidase inhibitors is reversible, and the conversion of carbohydrates to glucose is only delayed and not completely blocked.
- Glycosidase inhibitors have good safety, are rarely absorbed into the blood, little effect on the liver and kidney.
CD BioGlyco has a professional development team to to help clients customize the development route and plan the entire project. Please feel free to contact us if you are interested in enzyme inhibitors.
Reference
- Schneider, J.P.; et al. Synthesis and glycosidase inhibition properties of calix[8]arene-based iminosugar click clusters. Pharmaceuticals. 2020, 13(11): 366.
For research use only. Not intended for any clinical use.
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