Core 1 Inhibitor Development Service at CD BioGlyco

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.

• High-throughput screening (HTS) service

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.

• Structural optimization service

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.

• Bioactivity assessment service

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)

Publication

Technology: Lectin blotting, Tandem mass spectrometry (MS/MS), Liquid chromatography

Journal: Cell Chemical Biology

IF: 9.039

Published: 2021

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)

Applications

• Anti-inflammatory disease research: The development of core 1 inhibitors interferes with the synthesis of sugar chains during inflammation, thereby exploring new strategies for the research of inflammatory diseases (such as rheumatoid arthritis, inflammatory bowel disease, etc.).
• Oncology research: Core 1 sugar chains play an important role in the metastasis and invasion of tumor cells. By inhibiting the synthesis of core 1 sugar chains, it interferes with the sugar chain modification on the surface of tumor cells, thereby hopefully preventing the growth and spread of malignant tumors.
• Immunomodulation: Sugar chains may affect cell-cell interactions and signaling. The development of core 1 inhibitors is applied to study the impact of sugar chains on immune regulation and explore new ways to regulate immune responses by interfering with sugar chain synthesis.

Advantages

• CD BioGlyco is equipped with advanced technology means, such as HTS technology, molecular synthesis means, structure-activity relationship studies, etc., to support the screening, design, and development of core 1 inhibitors.
• CD BioGlyco has a multidisciplinary team of scientists with innovative thinking and capabilities to design and develop novel core 1 inhibitors.
• We have excellent project management capabilities and effectively organize and execute core 1 inhibitor development projects, to ensure high-quality core 1 inhibitor is delivered on time.

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.