CD BioGlyco aims to provide strong support to clients in the development of Glycosylation Inhibitors. α-Mannosidase II is predominantly found in the Golgi, lysosomes, endoplasmic reticulum, and cytoplasm of eukaryotes. As a key glycosidase, it is involved in N-Glycan Modification Processes. Its catalytic process is Zn2+-dependent. Swainsonine inhibits its activity. α-Mannosidase II function abnormally causes structural changes in cell surface N-glycans, which affects cell growth and differentiation. α-Mannosidase II inhibitors are very necessary to be developed. We provide a one-stop service for the development of α-mannosidase II inhibitors. Our α-mannosidase II inhibitor development directions include but are not limited to the following.
Higher concentrations of substrate analogs may act as metabolic inhibitors. We will screen corresponding substrate analogs to inhibit the activity of α-mannosidase II by binding to it.
Swainsonine, mannostatin A, etc. are compounds that inhibit α-mannosidase II isolated from plants such as Astragalus stellatus. We screen plants and animals for natural compounds that inhibit α-mannosidase II. We have special screening tools to improve the efficiency of inhibitor development.
Swainsonine is an effective α-mannosidase II inhibitor. We are trying to synthesize swainsonine analogs and test their inhibitory effect on α-mannosidase II. We also try to screen and synthesize other oligosaccharides-based scaffolds, such as iminosugars.
Fig.1 Process for the development of α-mannosidase II inhibitors. (CD BioGlyco)
Technology: Natural product-inspired combinatorial chemistry (NPICC)
Journal: Chemical Science
IF: 8.4
Published: 2022
Results: In this study, a series of new bicyclic iminosugar-based scaffolds by NPICC were synthesized. An α-hGMII inhibitor was identified. Derivatisation using computation-guided synthesis (CGS) resulted in the synthesis of a compound with a strong inhibitory effect. The compound was tested and found to be inhibitory to hepatocellular carcinoma without affecting the storage of oligomannose in serum. This compound has a modulating effect on the catabolism of N-glycans.
Fig.2 The natural product-inspired discovery of new selective α-hGMII inhibitors. (Chen, et al., 2022)
CD BioGlyco has extensive knowledge and experience in the development of Glycosidase Inhibitors, etc. We aim to provide efficient and high-quality inhibitor development services for our clients of glycosylation research. Please feel free to contact us to learn more about the detailed protocols and experimental procedures for inhibitor development.
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