GP is an allosteric enzyme that plays a key role in glycogen catabolism to catalyze the phosphorylation reaction. GP exists in two different forms that are converted to each other, such as phosphorylated versus non-phosphorylated forms, and high substrate affinity versus low substrate affinity. Therefore, the development of GP inhibitors is considered to be an effective target for the treatment of abnormalities in glycogen metabolism. Combining click chemistry, CD BioGlyco provides professional GlycoCLICK™-based Drug Development services. We have extensive experience in developing GlycoCLICK™-based Enzyme Inhibitors and Carbohydrate Click-based Lectin Ligands. We provide GP inhibitor design, synthesis, and enzyme inhibition assay services for our clients.

GP inhibitor synthesis service

Our researchers use click chemistry to synthesize many different GP inhibitors such as sugar-nucleoside and oleanolic acid-nucleoside conjugates, triazole derivatives, and oleanolic acid dimers.

Carbohydrate-derived triazoles: We provide a simple and convenient service for the synthesis of triazole derivatives. In the presence of copper (I), we synthesize differently protected triazole carbohydrates via 1,3-dipolar cycloaddition reactions to prop-2-yn-1-ol.
Oleanolic acid dimers: We provide highly efficient dimer synthesis services obtained through amidification, esterification, and Cu-catalyzed Huisgen dipolar cycloaddition reaction.

Enzyme inhibition assay

For the synthesized derivatives, we evaluate enzyme inhibition assays against rabbit muscle glycogen phosphorylase a (RMGPa) and glycogen phosphorylase b. Our researchers measure and compare the inhibitory abilities of the derivatives.

Schematic diagram of GlycoCLICK™-based GP inhibitor development service. (CD BioGlyco)

Publication

Technology: Click chemistry, Copper(I)-catalyzed Huisgen cycloaddition reaction, Enzyme inhibition assay

Journal: Synthesis

Published: 2010

Results: In this study, researchers used click chemistry to synthesize novel nucleoside conjugates with uridine and N-acetylglucosamine or oleanolic acid derivatives. Uridine was converted to the azide derivative by activation of methanesulfonic acid and nucleophilic substitution with sodium azide. The desired compounds were then obtained by copper(I)-catalyzed Huisgen cycloaddition reaction, and finally, the conjugates were synthesized by cycloaddition reaction. Furthermore, enzyme inhibition assay of the synthesized conjugates revealed that these new molecules are potential glycogen phosphorylase inhibitors.

Fig.1 Structure of synthetic nucleoside conjugates inhibitor. Fig.1 Structure of sugar-nucleoside conjugates. (Cheng, et al., 2010)

Applications

GP inhibitors are promising and targets for the effective development of potential novel antidiabetic agents for the treatment of type 2 diabetes.
GP inhibitors are involved in the development of other diseases associated with GP activity, such as cardiovascular disease and tumor growth.
GP inhibitors promote glycogen in its synthesis while controlling its overaccumulation.
GP inhibitors play a key inhibitory role in glucagon-induced glycogenolysis in hepatocytes.

Advantages of Us

Based on the activity characteristics of different enzymes, we provide professional inhibitor development route planning services.
Our highly experienced synthesis group synthesizes GlycoCLICK™-based GP inhibitors with high efficiency.
Analytical and test data involved in the development are delivered to the clients.

Combining click chemistry, CD BioGlyco provides professional GlycoCLICK™-based drug development services including GlycoCLICK™-based enzyme inhibitor and carbohydrate click-based lectin ligand development services. Our serious attitude and high-quality service have been recognized by our customers all over the world. Please feel free to contact us.

References

Ben Hamadi, N. Mechanochemical synthesis and reactivity of 1, 2, 3-triazole carbohydrate derivatives as glycogen phosphorylase inhibitors. Current Organic Synthesis. 2021, 18(4): 406-410.
Cheng, K.; et al. Synthesis of oleanolic acid dimers as inhibitors of glycogen phosphorylase. Chemistry & Biodiversity. 2010, 7(3): 690-697.
Cheng, K.; et al. Synthesis of nucleoside conjugates as potential inhibitors of glycogen phosphorylase. Synthesis. 2010: 1046-1052.

For research use only. Not intended for any clinical use.

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