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:
Fig.1 Glycan acetylation inhibitor development. (CD BioGlyco)
Technology: Chemical synthesis and inhibitor development
Journal: Journal of Biological Chemistry
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)
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.