The addition of N-acetylgalactosamine (GalNAc) to the serine or threonine of a polypeptide initiates O-glycosylation, which is further refined at the C3 or C6 position to form the core O-linked glycan structure. The core 4 structure is achieved by adding N-acetylglucosamine (GlcNAc) to the 6 bits of GalNAc in the core 3 structure. This process is catalyzed by core 4 β1,6-GlcNAc transferase. CD BioGlyco has various Glycosylation Inhibitor Development Solutions, and we provide a one-stop core 4 inhibitor development service.
CD BioGlyco uses computer-aided drug design and organic synthesis technology to design and synthesize compounds with core 4 inhibitory activity.
CD BioGlyco uses an efficient HTS means to identify candidates with core 4 inhibitory activity through large-scale screening of compound libraries. We have developed some inhibitors of core 4 β1,6-GlcNAc transferase, such as O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino-N-phenylcarbamate (PUGNAC), which is a competitive small molecule compound that interferes with the activity of core 4 enzymes, thereby inhibiting the transfer of β1,6-GlcNAc.
CD BioGlyco uses medicinal chemistry methods to optimize the structure of the screened candidates to improve their activity, selectivity, and pharmacokinetic properties.
CD BioGlyco uses a variety of in vitro and cellular assays to evaluate the inhibitory effect of candidates on core 4 and determine their inhibitory mechanisms.
CD BioGlyco provides pharmacokinetic evaluation services on drug metabolism, absorption, distribution, and excretion of candidates to determine the properties and potential toxicity of the candidates, including studies on in vitro metabolic stability, cell permeability, and in vivo kinetics.
Fig.1 Core 4 inhibitor development service. (CD BioGlyco)
Technology: Liquid chromatography analysis
Journal: Journal of Biological Chemistry
Results: The authors explored the reasons for the changes in O-GlcNAc levels observed in HT29 cells. The results showed that the increase in O-GlcNAc levels induced by PUGNAc is due to the direct inhibition of O-GlcNAcase in these cells. PUGNAc is a competitive inhibitor of O-GlcNAcase and it has a significant impact on the activity of O-GlcNAcase in HT29 cells. The inhibited concentration dependence was closely related to the concentration required to achieve maximum effect in cells.
Fig.2 Schematic diagram of PUGNAc inhibiting O-GlcNAcase. (Haltiwanger, et al., 1998)
CD BioGlyco is a biotechnology company with strong scientific research capabilities. We have established advanced laboratory facilities, HTS means, and drug design tools to conduct a rapid and effective core 4 inhibitor development process. Please feel free to contact us if you are interested in our inhibitor development service.