In mammals, one or more glycans are covalently bound to glycoproteins and proteoglycans or lipids to form a large number of complex glycans. These complex glycans not only form glycocalyx on the cell surface to provide support and organization to tissues, but also participate in cell adhesion, transduction, and intermolecular interactions. Research has found the consequences of abnormalities in the biosynthesis of many complex glycans in a variety of diseases, including vascular disease, infectious diseases, and cancer. At CD BioGlyco, we focus on studying the effects of molecules on the biosynthetic machinery of complex extracellular mammalian glycosylation, thereby Developing Glycosylation Inhibitors to modulate abnormalities of glycan biosynthesis in disease.
N-Glycosylation begins in the endoplasmic reticulum (ER), adding N-acetylglucosamine-P (GlcNAc-P) to polyol-P (Dol-P), and then under the action of GlcNAc transferase (GlcNAcT), mannosyltransferase (ManT), glucosyltransferase (GlcT) respectively, other monosaccharides are added to the end of the non-reduced nascent chain to form a 14-residue oligosaccharide precursor (Glc3Man9GlcNAc2-dolichol). Then, the oligosaccharyltransferase (OST) complex mediates the transfer of oligosaccharide precursors from the lipid carrier to the target protein. As the protein folds, α-glucosidase and α-mannosidase trim the glycan to form Man5GlcNAc2Asn. With years of accumulated knowledge and experience, we provide clients with N-glycan processing enzyme inhibitor development services, including OST inhibitor development services, α-glucosidase I inhibitor development services, α-glucosidase II inhibitor development services, α-mannosidase I inhibitor development services, α-mannosidase II inhibitor development services.
Our strategies for N-glycosylation processing enzyme inhibitor development:
Many natural products inhibit the processing of glycosidases during N-glycans synthesis, especially α-glucosidase and α-mannosidase, thereby blocking N-linked glycosylation. Since these bioactive compounds act early in the biosynthetic pathway, a lack of specificity affects their further development. Based on our client's needs, we modify the structure of this compound to develop analogs that specifically recognize processing enzymes in the glycosylation process.
Technology: Development of α-glucosidase inhibitors and study of anti-tumor activity in vitro
Journal: Heterocyclic Communications
IF: 2.0
Published: 2018
Results: The authors used coumarin-benzothiazole hybrids as the core to design α-glycosidase inhibitors 5a-c and analyzed the antioxidant and anti-tumor activities of 5a-c. The results showed that compound 5c had high activity against central nervous system cancer and ovarian cancer, with half-maximal growth inhibition (GI50) values of 0.24 and 0.33 μM, respectively. The authors also measured the inhibitory activity of 5a-c on α-glucosidase. The substitution of coumarin in the new hybrid molecule has a great impact on compounds 5a-c, which is beneficial to the development of new analogs with better biological activity based on the research in this article.
Fig.1 Structure of compound 5a-c and interaction of compound 5c with the binding site of the target enzyme. (Gabr, 2018)
With advanced technology and years of accumulated experience, CD BioGlyco provides comprehensive N-Glycosylation Inhibitor Development Services for clients around the world. If you have any research needs, please contact us in time and we will provide you with a satisfactory plan for your evaluation.
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