Galectin proteins have been targets of interest in numerous therapeutic areas for some time. Galectin-3 has been identified as a target of particular interest because of its unique structural characteristics and physiological profile. Recent literature indicates galectin-3 inhibition can decrease myofibroblast activation and procollagen expression with the potential to affect the progression of fibrosis in the lung, liver and kidney. Potential π-stacking interactions between one monosaccharide ligand bound to the carbohydrate recognition domain of a galectin-3 protein and a second ligand bound to a different galectin-3 protein molecule were observed in the extended crystalline lattice in an X-ray crystal structure obtained while studying the monosaccharide structure-activity relationship. The direct interaction between the ligands suggests a potential for dimeric galectin-3 inhibitors which bind to two galectin-3 molecules simultaneously. This work describes the exploration of dimers designed to further probe these observations and explore the potential of binding to dimeric or higher order multimeric galectin-3 assemblies.
CITATION STYLE
Swidorski, J. J., Beno, B. R., Liu, C., Yoon, D. S., Ghosh, K., Sale, H., … Regueiro-Ren, A. (2023). Discovery and exploration of monosaccharide linked dimers of galectin-3 inhibitors to target fibrosis. Medicinal Chemistry Research, 32(7), 1453–1480. https://doi.org/10.1007/s00044-023-03087-x
Mendeley helps you to discover research relevant for your work.