Glutamine: Fructose Amidotransferase Inhibitor Development Service at CD BioGlyco

Glycosylation inhibitors are undergoing rapid development and CD BioGlyco is committed to the development of various types of Glycosylation Inhibitors. These include N-Glycosylation Inhibitor Development, and O-GlcNAc Inhibitor Development, among others. In O-GlcNAc inhibitor development, we provide systematic glutamine: fructose amidotransferase inhibitor development service to our clients.

• Modeling-molecular docking analysis method
  CD BioGlyco utilizes a combination of pharmacophore modeling, homology modeling, and molecular docking analysis to develop novel glutamine: fructose amidotransferase competitive inhibitors.
  • In the first step, we used kinetic experiments to design pharmacophore models of glutamine: fructose amidotransferase inhibitor. Then, we utilize the 3D-quantitative structure-activity relationship technique to analyze their biological activity (inhibitory activity). Finally, screening is performed using databases to characterize the activity of the inhibitors.
  • In the second step, homology modeling is performed to construct the glutamine binding site of fructose: amidotransferase protein. The modeled active sites are used to dock the molecules under research to probe important receptor-ligand interactions and to screen molecules that are available as inhibitors according to the hierarchical virtual screening (HVS) database.
• Screening-biological analysis method
  • A full-length fragment of the glutamine: fructose amidotransferase gene by amplifying it from the cDNA of human liver tissue, we express the glutamine: fructose amidotransferase protein in Escherichia coli. The glutamine: fructose amidotransferase protein with high purity is obtained by affinity chromatography column with nickel ion chelate column.
  • The catalytic activity of recombinant glutamine: fructose amidotransferase protein is detected according to kinetic experiments.
  • Using recombinant glutamine: fructose amidotransferase protein, an in vitro screening method for glutamine: fructose amidotransferase inhibitors is established. And screened glutamine: fructose amidotransferase inhibitor with higher inhibitory activity.

Fig.1 Glutamine: fructose amidotransferase inhibitor development methods. (CD BioGlyco)

Publication

Technology: Pharmacophore and docking-based hierarchical virtual screening protocol

Journal: SAR and QSAR in Environmental Research

IF: 3

Published: 2013

Results: Using a combination of pharmacophore modeling, homology modeling, and molecular docking analysis, this research designed novel human glutamine: fructose-6-phosphate amidotransferase (GFAT) competitive inhibitors and explored important interaction details of the inhibitor molecules. Pharmacophore models of the GFAT inhibitors were developed and subsequently validated and screened using the database to identify the novel molecules. Homology modeling was then performed to construct glutamine binding sites for GFAT proteins. The simulated active sites were used to dock the molecules under research and the molecules screened against the database were scrutinized based on basic interactions. This systematic computer simulation scheme helped the authors identify new molecules for the treatment of type II diabetes and its complications.

Fig.2 Molecular structures of reported GFAT inhibitors. (Vyas, et al., 2013)

Applications

• Glutamine: fructose amidotransferase inhibitor serves as a novel target for insulin sensitization, and it can be used to delve into the treatment of insulin resistance combined with disorders of lipid metabolism.
• Glutamine: fructose amidotransferase inhibitor can be used to investigate the development of diabetes and its vascular complications.
• Glutamine: fructose amidotransferase inhibitor can be used to research agents to improve lipid metabolism.

Advantages

• We have custom R&D solutions.
• We develop glutamine: fructose amidotransferase inhibitor with high purity.
• We have excellent process development, optimization, and scale-up technologies.

CD BioGlyco constructs a comprehensive glycosylation inhibitor development platform. We offer a wide range of inhibitor development routes and custom inhibitor development solutions for our clients. We are constantly updating our technology to provide high-quality R&D services to our clients. If you are interested in our services, please feel free to contact us.