High-quality Services at CD BioGlyco

Glycosylation inhibitors play an obvious role in the therapeutic research of diseases. CD BioGlyco has constructed an inhibitor development platform, which is dedicated to the Development of Glycosylation Inhibitors, and provides a wide range of inhibitor development services, such as O-N-acetylglucosamine (O-GlcNAc) transferase inhibitor development service.

• Exploration of O-GlcNAc transferase
  O-GlcNAc transferase is present in mammals and contains at least three isoforms. At CD BioGlyco, we utilize in vitro experiments to determine the peptide structure and protein recognition propensity of each isoform. The specific recognition of the substrate by the transferase is determined using peptide repeat sequence removal experiments. In addition, the crystal structure of O-GlcNAc transferase is determined by X-single-crystal diffraction to probe its reaction site.
• Development of inhibitors
  A prerequisite for the development of O-GlcNAc transferase inhibitors is an activity assay. At CD BioGlyco, we offer activity assays such as conventional methods and high-throughput assays.
  
  • Conventional method
    We measure O-GlcNAc transferase activity by liquid scintillation spectroscopy and fluorography using radiolabeled glycosyl donor substrates. Next, we utilize GlcNAc to remediate the glycosamine biosynthesis pathway to synthesize glycosidic acid analogs and use this method to measure glycosidic acid inhibitory activity. For the in vivo activity of the inhibitors, we use Western blot analysis.
  • High-throughput activity assay method
    We utilize fluorescent substance displacement assays and a "protease-protection" strategy to rapidly screen different libraries for O-GlcNAc transferase inhibitors.
  In addition, we will use O-GlcNAc transferase as a template to enable the self-assembly of suitable constructs using in situ click chemistry for target-directed synthesis of highly active inhibitors to avoid dependence on high-throughput activity assays.

Fig.1 Development content of O-GlcNAc transferase inhibitor. (CD BioGlyco)

Publication

Technology: Bundled in situ click chemistry

Journal: Journal of Medicinal Chemistry

IF: 7.3

Published: 2016

Results: In this research, the authors utilized bundled in situ click chemistry (TISCC), using p-azidoiodoacetanilide as a bifunctional building block M. Sixty-one alkyne-based building blocks N were screened, and two cell-permeable O-GlcNAc transferase (OGT) inhibitors (APNT and APBT) were developed after subsequent chemical modifications. These two inhibitors were able to reduce O-GlcNAc glycosylation levels in cells without significant cytotoxicity. The unusual non-competitive inhibition for OGT contributes to the discovery of new inhibitors and the exploration of the regulatory mechanisms of OGT.

Fig.2 TISCC: (a) Screening of building blocks to discover the new candidate; (b) Synthesis of the new candidate for activity evaluation. (Wang, et al., 2016)

Applications

• O-GlcNAc transferase inhibitor can be used to probe the function and regulatory mechanism of O-GlcNAc glycosylation.
• O-GlcNAc transferase inhibitor can be used to develop therapeutic agents for related diseases such as tumors, diabetes, cardiovascular diseases, and neurodegenerative diseases.
• The development of the O-GlcNAc transferase inhibitor can be used to explore the regulation of the pentose phosphate signaling pathway, glycogen synthesis signaling pathway, and so on.

Advantages

• We provide a large number of different kinds of O-GlcNAc inhibitor development services available for clients to choose from.
• The O-GlcNAc transferase inhibitor developed by us is characterized by high purity and high selectivity.
• We provide custom inhibitor development solutions according to the client's needs.

CD BioGlyco's glycosylation inhibitors are designed for specific research purposes or as a reference for a wide range of bioscience applications. We provide a wide range of glycosylation inhibitor development services and are always committed to serving researchers in different fields. At the same time, every program we develop is quality-tested to ensure client satisfaction. If you are interested in our services, please feel free to contact us.