α-Glucosidase I Inhibitor Development Service at CD BioGlyco

During N-glycosylation, α-glucosidase I is a key member of glycan biosynthesis and selectively catalyzes the removal of newly generated terminal glucose from glycoproteins. Inhibition or loss of α-glucosidase I prevents further trimming of glycoproteins. Studies have shown that inhibiting α-glucosidase I activity makes viruses such as influenza and hepatitis less infective. Although many corresponding inhibitors have been developed, they lack specificity, resulting in undesirable side effects. For many years, CD BioGlyco has been focusing on glycobiological research and has accumulated extensive knowledge and experience. We combine the structure and catalytic mechanism of α-glucosidase I to provide clients with the development services of specific α-glucosidase I inhibitors. Our service process is as follows:

• Study on the structure and catalytic mechanism of α-glucosidase I

α-Glucosidase I is a member of the glycoside hydrolase (GH) family with a molecular weight of approximately 80-110 kDa. We use various software to analyze, compare, and predict the structure of the protein while constructing mutants and performing expression and structural characterization.

• Virtual screening of α-glucosidase I inhibitor

Study the interaction between α-glucosidase I and the substrate Glc₃Man₉GlcNAc₂-Asn. We use virtual screening based on molecular docking to identify compounds with new chemical types, provide target compounds for later synthesis, and make the development of inhibitors faster and more efficient.

• Synthesis of α-glucosidase I inhibitors
  • De novo synthesis: Based on the results of virtual screening, perform retrosynthetic analysis of the target compound, design a synthesis route, explore synthesis conditions, synthesize the target compound, and characterize its structure.
  • Structural modification: Studies the structure-activity relationship of reported inhibitors, and partial group modifications and transformations are performed to synthesize inhibitor analogs.
• Activity assay of α-glucosidase I inhibitors
  • In vitro activity assay: The compounds are screened for in vitro α-glucosidase I inhibitory activity and the IC₅₀ value is calculated. And study their in vitro cytotoxicity in the LO2 cell line.
  • In vivo activity assay: Determine the inhibitory activity of the target compound in mice, rats, and other animals.

Fig.1 α-Glucosidase I inhibitor development service. (CD BioGlyco)

Publication

Technology: Virtual screening, Activity assay

Journal: Frontiers in Chemistry

IF: 5.545

Published: 2021

Results: The authors screened 52 candidate compounds from the compound library through virtual screening of molecular docking, and analyzed the α-glycosidase inhibitory activity, fluorescence quenching, kinetic parameters, and cell activity. The results showed that these compounds bind to α-glycosidase and are non-competitive inhibitors. Among them, compound 44 has the best inhibitory activity against α-glycosidase and is a potential α-glycosidase inhibitor.

Fig.2 (A) α-Glycosidase inhibitory activity; (B) The chemical structures and IC₅₀ curves of partial compounds. (Liu, et al., 2021)

Advantages

• We research clients' targets and quickly screen potential compounds through virtual screening of molecular docking to accelerate the development of glycosylation inhibitors.
• We analyze the structure-activity relationship of compounds and modify and transform the structures of discovered inhibitors to develop compounds with higher activity.
• We also conduct de novo synthesis of target inhibitors according to the specific needs of clients, design synthesis routes, and optimize reaction conditions to develop optimal industrial routes.
• We test the activity of compounds, analyze structure-activity relationships, and continuously optimize and transform compounds.

CD BioGlyco is a leading global glycobiology company with extensive experience in the Development of Glycosylation Inhibitors. We are confident that we provide you with an optimal development solution that meets your needs. Please feel free to contact us for more development information.