Multiple effector pathways in (patho)physiology are controlled by the interaction of glycans and tissue lectins. The pro-degradative action of Galectins-1 and -3 (Gal-1 and -3) in the development of osteoarthritis (OA) via matrix metalloproteinases (MMPs), particularly MMP-13, is a clinically important example. It is possible to analyze the functions of lectins and proteolytic enzymes by creating heterobifunctional inhibitors that can directly block Galectin binding and MMPs as well as prevent their Galectin-dependent activation. CD BioGlyco provides Custom Carbohydrate Synthesis, Custom Glycoconjugate Synthesis, and Synthesis Process Development and Optimization for customers to help study the functions of new heterobifunctional inhibitors.
A key factor in OA, MMP-13 activity can be increased by Galectins (particularly Gal-1 and Gal-3), with the degrading of type II collagen driving the degenerative processes. Therefore, there is a clear need for the development of OA drugs that contain extremely powerful MMP-13 inhibitors as well as upstream components like Gal-3. Researchers offer a heterobifunctional inhibitor (compound 1) that interacts with matrix metalloproteinases and Galectins at the same time. Both MMP-13 inhibition and blocking Galectin binding to counterreceptors are possible with this substance. There are additional benefits to administering a drug that contains both a hydroxamic acid-based MMP inhibitor and Galectin-inhibiting sugar moieties. In the case of OA, the inhibitor can also prevent the portion of elevated MMP-13 activity brought on by causes other than Galectins. Intracellular Galectins can be neutralized (before release).
Fig.1 The structure of compound 1. (Manning, et al., 2022)
The ability to transport a bioactive material to the location of Galectin-sugar headgroup recognition is a subject compound's benefit. The in-situ activity of an effector downstream of lectin binding, i.e., the MMPs' destruction of OA cartilage, can be decreased as a result. Since more than one member of the Galectin protein family is implicated in the pathogenesis of OA, adding two binding sites as opposed to one glycan moiety to compound 1 is predicted to enhance avidity with the simultaneous binding of two Galectins, either two of the same or two distinct Galectins.
CD BioGlyco provides custom carbohydrate synthesis and glycoconjugate synthesis platforms for customers to study the novel heterobifunctional inhibitor. we have the confidence to meet customers’ needs for sciences research, if you are interested in our services, please contact us for more detailed information.
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