T antigen (Galβ1-3GalNAcα1-Ser/Thr) is the main core structure of mucin-type O-glycan, which is synthesized by transferring galactose (Gal) to N-acetylgalactosamine (GalNAc) through core 1 β1,3-galactosyltransferase (C1GalT1). Altered expression of C1GalT1 results in global changes in O-glycan structure in multiple glycoproteins. Core 1 is a common core structure in human red blood cells and most lymphocytes. Cosmc is a C1GalT1-specific molecular chaperone that is important for the activity of C1GalT1. As a leading biotechnology company, CD BioGlyco provides specialized core 1 inhibitor development services.
CD BioGlyco provides efficient HTS service. We test a large number of compounds using HTS technology to identify candidate compounds with core 1 inhibitory activity, including in vitro enzyme activity assays, cell models, or other biological detection methods.
CD BioGlyco provides synthesis, modification, and structure optimization for the initially screened compounds. We develop highly selective, high-affinity core 1 inhibitors through structure-activity relationship (SAR) studies and computer-aided drug design experiments. Ac5GalNTGc is a peracetylated C-2 thiol-substituted GalNAc that blocks the elongation of core 1 O-glycans in different cell types and is a potent inhibitor of mucin-type O-linked glycosylation. Ac5GalNTGc reduces the activity of C1GalT1, blocks the O-glycan structure at the Tn antigen stage, and reduces T-antigen formation and O-glycan elongation.
CD BioGlyco provides a candidate compound activity evaluation service. We evaluate the inhibitory activity and biological activity of structurally optimized candidate molecules through experimental studies in vivo animal models, cell function analysis, or other biological evaluation methods.
Fig.1 Core 1 inhibitor development service. (CD BioGlyco)
Technology: Lectin blotting, Tandem mass spectrometry (MS/MS), Liquid chromatography
Journal: Cell Chemical Biology
Results: The authors measured the extended glycan formation on the substrate after adding Ac5GalNTGc to the cell culture medium. Ac5GalNTGc reduced Gal incorporation into the substrate GalNAc-O-Bn. In enzymatic studies, after the authors cultured cells with Ac5GalNTGc, the β1,3GalT enzyme activity in HL-60 was reduced by approximately 40%, and the biosynthesis of core-1 glycans was also reduced.
Fig.2 Research results of Ac5GalNTGc on cell activity. (Wang, et al., 2021)
CD BioGlyco has deep technical expertise and rich experience in the field of Glycosylation Inhibitor Development. We are client-oriented and provide personalized core 1 inhibitor development service. Please feel free to contact us if you require specific service details.