Oligosaccharyltransferase Inhibitor Development Service
Oligosaccharyltransferase (OST) Inhibitor Development Service at CD BioGlyco
OST is a constitutive and unregulated multi-subunit enzyme complex that transfers completed oligosaccharides of N-glycosylation from dolichol precursors to aspartic acid (Asn) of target proteins. In mammalian cells, OST contains one of two individually encoded catalytic subunits, STT3A or STT3B. The study found that the deletion of OST subunits results in a more than 99% reduction in flavivirus infection in cell cultures, suggesting OST is a potential antiviral target. At CD BioGlyco, we have developed N-Glycosylation Processing Enzyme Inhibitor Development solutions and provide clients with high-quality inhibitor development services of OST, α-glucosidase, and α-mannosidase.
A cell-permeable N-linked glycosylation inhibitor 1 (NGI-1) has been reported that engages and blocks the activity of the OST catalytic subunit with higher specificity for STT3B. Based on our clients' OST inhibitor development needs, we synthesize and screen a series of NGI-1 analogs to improve their biological activity and enhance specificity for both catalytic subunits. Our process is as follows:
- Protocol design of OST inhibitor
Combining the development principles, structure-activity relationships, and interaction information with targets of OST inhibitors, a series of compounds are designed and the compounds are scored through computer virtual screening to screen out the target compounds.
- Synthesis and characterization of target compounds
Design the synthesis route of the target compound, optimize the synthesis conditions of the target compound, gradually synthesize a series of compounds, analyze the purity, and characterize and structure of the compounds by high-performance liquid chromatography (HPLC), mass spectrometry (MS), and nuclear magnetic resonance (NMR).
- Luciferase, proliferation, and viability assays
After treatment with target compounds, luciferase assays are performed in gene-edited cells to test the specific effects of target compounds on OST subunits (STT3A and STT3B). The average glycan occupancy of target compounds is analyzed in conjunction with western blotting.
- Structure-activity relationship of OST inhibitors
Combined with the results of proliferation and activity assays, we help clients analyze the impact of different groups on the biological activity of compounds.
- Epidermal growth factor receptor (EGFR) expression and functional analysis
To evaluate changes in EGFR N-linked glycosylation receptor localization and function when cells are treated with OST inhibitors.
Fig.1 OST inhibitor development service. (CD BioGlyco)
Publication
Technology: Gene editing, Western blot analysis
Journal: Cell Discovery
IF: 38.09
Published: 2021
Results: The authors screened host factors that interact with four structural proteins in SARS-CoV-2 (spike protein, envelope protein, membrane protein, and nucleocapsid protein). Authors found that the OST complex interacts with spike protein, envelope protein, and membrane proteins are closely related, and blocking OST significantly inhibits the infection of SARS-CoV-2 and its variants. Next, the authors studied whether OST is used as a potential target of SARS-CoV-2 and the antiviral effect of OST inhibitors in human colorectal adenocarcinoma cells. The results indicate that the OST inhibitor NGI-1 is used as a broad-spectrum anti-coronavirus drug.
Fig.2 Biological network cluster of N-linked glycosylation. (Huang, et al., 2021)
Advantages
- According to the development needs of inhibitors, our scientists will communicate with you to design experimental plans and adjust the plans at any time according to your needs.
- Before compound synthesis, we perform virtual screening to select potential compounds to speed up the development of inhibitors.
- Combined with the activity screening results, the structure-activity relationship of the compounds is analyzed, and the compounds are continuously optimized.
CD BioGlyco provides efficient, high-quality, and worry-free Glycosylation Inhibitor Development solutions to clients around the world. Upon project completion, we will deliver a complete product and project report. If you have inhibitor development needs, please do not hesitate to contact us and we will provide you with the best solution.
Reference
- Huang, Y.J.; et al. Identification of oligosaccharyltransferase as a host target for inhibition of SARS-CoV-2 and its variants. Cell Discovery. 2021, 7(1): 116.
