Glycan Acetylation Inhibitor Development at CD BioGlyco

Glycans acetylation plays a crucial role in human immunology, disease pathogenesis, and cancer progression. When acetylation is abnormal, it leads to disease. CD BioGlyco is dedicated to the Development of Glycosylation Inhibitors, and in the area of glycan acetylation inhibitor development, we provide services that include, but are not limited to:

• Screening of inhibitors of glycan acetylation
  When glycans undergo acetylation, it is acetyltransferase that plays a key role. To inhibit the acetylation of glycans, inhibition of the enzyme activity is an effective method. Acetyltransferases usually interact with sites on serine residues, based on this feature, we use glycosides as well as basic methods of chemical modification to selectively target serine residues to inhibit the catalytic activity of acetyltransferases. We also utilize high throughput screening techniques for further development and screening of glycosides to identify compounds that effectively interfere with the activity of acetyltransferases.
  We design and optimize the small molecule compounds obtained from the screening to develop glycolysis inhibitors with good inhibitory ability.
• Bioactivity testing of glycan acetylation inhibitors
  We provide cell or animal models to evaluate the inhibitory effect and safety of the developed molecules using techniques such as enzyme-linked immunosorbent assay (ELISA), Western blotting, and flow cytometry to determine their mechanism of action on acetyltransferases.

Fig.1 Glycan acetylation inhibitor development. (CD BioGlyco)

Publication

Technology: Chemical synthesis and inhibitor development

Journal: Journal of Biological Chemistry

IF: 5.5

Published: 2021

Results: The synthesis of C-9-N-acetylsalivaryl α-methylglycosides and their characterization as influenza C virus (ICV HEF) esterase inhibitors are reported first. The molecule mimics 9-O-acetylsalivaryl, a substrate of ICV HEF, with an inhibition constant of about 2.8 mM. Next, a more potent inhibitor is developed by mimicking the formation of the oxyanion intermediate state following a catalytic nucleophilic attack on serine. For this purpose, methyl phosphodiester is installed at the C-9 position of sialic acid. The observed inhibition constant is only 2 mM. To research the effect of the glycosidic ligand on inhibitory potency, α-propyl salicyl glycoside derivatives are prepared with little improvement. Despite the lack of potency and selectivity of these inhibitors, improvements in the basic approach using sialic acid glycosides and chemical modifications may allow selective targeting of bacterial and viral sialic acid-specific O-acetyl esterases (SIAE). Further development and screening of sialic acid glycoside libraries may identify lead compounds that effectively interfere with SIAE activity, and further structure-directed optimization may yield high-affinity inhibitors.

Fig.2 Exoenzymatic installation of O-acetylated sialic acids to cell surface glycans and overview of SIAE inhibitors. (Visser, et al., 2021)

Applications

• The glycan acetylation inhibitors can be used to research organ- and cell-type-specific expression and specific interactions. Examples include cellular interactions with influenza viruses.
• The glycan acetylation inhibitors can be targeted to mammals or bacteria and thus are used in research on antiviral therapy.
• Inhibitors of glycan acetylation can be used to affect specific molecular recognition events such as intermolecular binding and degradation.

Advantages

• Our inhibitor development services cover a wide range of areas to ensure effective solutions to our client's challenges in inhibitor development.
• Our research protocols provided by our professionals have undergone systematic quality testing and are highly reliable.
• We use all glycans as research targets, which makes it easy to explore new acetylation sites.

CD BioGlyco has a strong platform of glycobiology resources dedicated to the development of glycosylation inhibitors. Our professional researchers keep abreast of the trends in science and technology and update our experimental techniques to ensure our clients' satisfaction. If you are interested in our services, please feel free to contact us.

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