Carbohydrate Click-based Galectin Inhibitor Development Service

Carbohydrate Click-based Galectin Inhibitor Development Service

Powering Precision with Carbohydrate Click for Next-Gen Galectin Inhibitors

Galectins act through a "receptor"-"ligand" mechanism during apoptosis and metastasis of tumor cells. The use of carbohydrates to develop relevant inhibitors effectively interferes with the galectin and ligand binding pathway. At CD BioGlyco, we provide systematic Lectin Ligand Development Services that are effectively integrated with Drug Development Services. Here, we provide our clients with high-quality carbohydrate click-based galectin inhibitor development services.

We utilize Cu(I)-assisted cycloaddition reactions of alkynes and azides to generate linear oligogalactopyranosides and use them to construct libraries of galectin inhibitors. The conditions throughout the reaction are mild and efficient, no protecting groups are required, and purification is not necessary in most cases.

  • In the first stage of library synthesis, we utilize click chemistry to generate functionalized ketocarboxylic acids containing different alkynes. Then, the compounds in the library are tested for preliminary inhibitory activity, and the binding sites of the compounds on the carbohydrate recognition domain of galectin are analyzed, and compounds with high inhibitory activity against galectin are screened in a high-throughput manner.
  • In the second stage, we continued to utilize click chemistry to bind the compounds screened in the previous step to the alkyne library assembly. Then, large libraries of efficient galectin inhibitors are constructed. Due to the efficiency of the click reaction and the water compatibility, in most cases, the assembled products can be screened directly as inhibitors without any purification.

Throughout the process, we provide animal models or cellular models for in vitro experiments to analyze the inhibitory activity and semi-inhibitory concentration values of galectin inhibitors in the library. We also provide fluorescent labeling methods to analyze the binding sites of compounds in the inhibitor library to the carbohydrate recognition domain (CRD) of galectin.

Fig.1 Galectin inhibitor development. Fig.1 Process of developing galectin inhibitors based on carbohydrate clicks. (CD BioGlyco)

Publication Data

Technology: Click chemical methods, X-ray crystallography

Journal: Chemical Biology & Drug Design

IF: 3.0

Published: 2020

Results: The authors synthesized a linear oligogalactoside by simple click chemistry. Not only does it mimic the polygalactosamine sequence expressed on the surface of eukaryotic cells, but it is also capable of specifically recognizing the extracellular form of galectin 3. The next authors describe the X-ray crystal structure of the galactoglucan lectin 3 CRD in complex with synthesized di- and tri-galactopyranosides, confirming the binding of these compounds within the carbohydrate-binding site. Initial structures indicate that binding interactions occur primarily in the galactose portion of the nonreducing end, mainly in the C and D sites of the CRD. In contrast to oligogalactosamine, the latter binds more consistently throughout the groove formed by the five substituents of the galactagogue 3 CRD.

Applications

  • Galectins are involved in the regulation of cell growth and differentiation and are closely related to the whole process of tumor formation, development, and metastasis. Therefore, galectin inhibitor development can be used for further development of antitumor and anticancer drugs.
  • Carbohydrate click-based development of galectin inhibitors can be used to explore the function of galectin in signaling, and other biological processes produced.

Advantages

  • We offer inhibitor development technology for a wide range of applications with high yields and strong stereoselectivity.
  • We offer large-scale production of inhibitor products and our products are highly stable.
  • We have a professional inhibitor development team and provide custom inhibitor development solutions.

CD BioGlyco has extensive experience in click chemistry research. With our first-class click chemistry technology, we provide our clients with high-quality drug development services. For example, inhibitor development, antagonist development, and so on. If you are interested in our click chemistry services, please feel free to contact us.

References

  1. Dussouy, C.; et al. Linear triazole-linked pseudo oligogalactosides as scaffolds for galectin inhibitor development. Chemical Biology & Drug Design. 2020, 96(4): 1123-1133.
  2. Thirumurugan, P.; et al. Click chemistry for drug development and diverse chemical-biology applications. Chemical Reviews. 2013, 113(7): 4905-4979.
For research use only. Not intended for any clinical use.
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