Core 1 branches through the core 2 β1,6-N-acetylglucosaminyltransferase (C2GnT) family to form core 2, and core 2 O-glycans serve as scaffolding structures for sialyl-Lewis x. High levels of C2GnT contribute to the increase in core 2 O-glycan structure, which plays a key role in cell adhesion and cell migration. CD BioGlyco provides mature core 2 inhibitor development service.
CD BioGlyco uses efficient high-throughput screening technology and computational methods to screen potential target enzyme inhibitor candidates from our compound library.
CD BioGlyco will conduct structure-activity relationship studies on the screened enzyme inhibitors, and our scientists will design and synthesize new core 2 inhibitor candidates and optimize their pharmaceutical properties. We have developed a potent C2GnT1 inhibitor, the substrate Galβ1-3GalNAcα-p-nitrophenyl (PNP), which acts as an effective inhibitor of C2GnT1 under UV irradiation at 350 nm. We have verified that other PNP-sugar derivatives also act as specific inhibitors of C2GnT1. In addition, we also have developed a divalent imidazolium salt compound, which is a new class of glycosyltransferase inhibitors that selectively inhibits the synthesis of core 2.
CD BioGlyco evaluates the biological activity, selectivity, and toxicological properties of core 2 inhibitors through specialized in vitro cell and animal model experiments. We also provide core 2 inhibitors research service on the mechanism of action including cell signaling pathway analysis or protein interaction research.
Fig.1 Core 2 inhibitor development service. (CD BioGlyco)
Technology: Western blot analysis
Journal: Biochimica et Biophysica Acta (BBA)-General Subjects
Results: The authors expressed recombinant soluble human galactose (Gal) and N-acetylglucosamine (GlcNAc) transferases that synthesize O-glycan core 2. The authors determined the properties and substrate specificity of the enzyme using synthetic receptor substrate analogs and tested them as inhibitors. The results showed that imidazolium salt effectively inhibited C2GnT1.
Fig.2 Inhibition of human C2GnT1 with different concentrations of bis-imidazolium salt inhibitors. (Gao, et al., 2013)
CD BioGlyco has established reliable Glycosylation Inhibitor Development Solutions, and we tailor the core 2 inhibitor development strategy according to client needs. Please feel free to contact us promptly if you would like to inquire about specific inhibitor development content.