α-Glucosidase II Inhibitor Development Service at CD BioGlyco

Glycoproteins in the early secretory pathway need to undergo quality control, and the endoplasmic reticulum (ER) happens to be a complex protein quality control system. In this system, Glc₃Man₉GlcNAc₂ with three non-reducing end branches (D1, D2, and D3) serves as an oligosaccharide precursor attached to the nascent protein. Among them, the D1 end removes the outermost α1,2 glucose under the action of glucosidase I. Glucosidase II then sequentially trims the remaining two terminal glucose residues. Complete deglycosylation by glucosidase promotes glycoprotein detachment from chaperone complexes and transport to the Golgi apparatus. Unfolded glycoproteins are not re-glycosylated. Therefore, glucosidase I and glucosidase II are very important for N-glycosylation processing of proteins. CD BioGlyco relies on years of glycosylation knowledge accumulation and inhibitor development experience to provide clients with α-glucosidase II inhibitor development services for targeting a variety of diseases. Our strategies are as follows:

• Plant extracts as a source of α-glucosidase II inhibitor

Explore the inhibitory activity of natural extracts from different plant sources on α-glucosidase II, such as terpenoids, flavonoids, chalcone derivatives, etc. We extract, isolate, purify, and characterize natural compounds from target plants and determine α-glucosidase inhibitory activity, pharmacokinetic parameters, and toxicity.

• Chemical synthesis as a source of α-glucosidase II inhibitors

Based on your needs, we design, synthesize, characterize, and evaluate new α-glucosidase II inhibitors, and perform homology modeling and molecular docking studies to analyze the interaction of the compounds with the active site.

• Chemical modifications as sources of alpha-glucosidase II inhibitors

We analyze the structure-activity relationships and site-related effects of reported inhibitors and use chemical methods to structurally modify and transform reported compounds to optimize biological activity and pharmacokinetic parameters.

Fig.1 Strategies for α-glucosidase II inhibitor development. (CD BioGlyco)

Publication

Technology: Kinetic studies, Docking model

Journal: Glycobiology

IF: 4.3

Published: 2019

Results: The authors studied the effects of nine iminosugars on the effects of α-glucosidase I and α-glucosidase II. As a result, five iminosugars that selectively inhibit N-glycan trimming were screened out. Among them, 3,7a-di-epi-alexine is a selective inhibitor of α-glucosidase I, and 1,4-dideoxy-1,4-imino-D-arabinitol is the most effective selective inhibitor of α-glucosidase II. The authors also used modeling to study the interaction of 1,4-dideoxy-1,4-imino-D-arabinitol with the active site of α-glucosidase II.

Fig.2 The effect of compounds on α-glucosidase II enzyme activity. (O'Keefe, et al., 2019)

Advantages

• With many years of glycosylation knowledge accumulation and inhibitor development experience, we provide clients with α-glucosidase II inhibitor development services for various diseases such as diabetes, cancer, and viral infections.
• We not only extract and purify active compounds from plants, but we also synthesize potential α-glucosidase II inhibitors through chemical synthesis and chemical modification.
• We measure the biological activity of target compounds and combine computer simulations of the interactions between compounds and biologically active sites.

CD BioGlyco has a large team of scientists and a comprehensive development strategy and is committed to working with clients around the world to provide top-notch Glycosylation Inhibitor Development solutions. If you are interested in our inhibitor development, please feel free to contact us for more details.