The Research Group of Bioorganic Chemistry and Biomaterials at the ICPF of the CAS led an interdisciplinary research team that developed a new class of human galectin-1 inhibitors based on organoruthenium complexes. The results were published in the Journal of Medicinal Chemistry.
Galectin-1 is a protein that interacts with certain carbohydrates on the cell surface and plays an important role in the regulation of immune responses and the tumor microenvironment. Increased activity of this protein can promote tumor growth and suppress antitumor immunity, making it an attractive target for the development of new therapeutic agents. However, the development of selective inhibitors is challenging because the binding sites of individual galectins are structurally very similar. The research team therefore designed new inhibitors based on the disaccharide thiodigalactoside, which was modified with an organoruthenium arene complex. This unusual combination of carbohydrate chemistry and organometallic structures resulted in compounds with nanomolar affinity and exceptionally high selectivity for galectin-1—the affinity for galectin-1 is up to three orders of magnitude higher than for the related protein galectin-3.
The most potent compounds were able to block the binding of galectin-1 to the surface of tumor cells and prevent galectin-1-induced deactivation of T-lymphocytes. These results demonstrate that organoruthenium glycomimetic structures represent a promising strategy for the development of selective galectin inhibitors with potential applications in anticancer therapy.
Researchers from the Masaryk Memorial Cancer Institute, the Institute of Biophysics of the Czech Academy of Sciences, the Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, and the Institute of Microbiology of the Czech Academy of Sciences also contributed to the study.
- Hamala V., Kurfiřt M., Červenková Šťastná L., Dvořák F., Bernášková J., Sýkorová A., Kozák J., Zavřel M., Staroňová T., Šebest P., Ostatná V., Červený J., Bojarová P., Holčáková J., Hrstka T., Hrstka R., Karban J.: Organoruthenium Glycomimetics Exhibit High Selectivity and Nanomolar Affinity for Human Galectin 1. J. Med. Chem. 2026, 69(4), 4789-4809. doi.org/10.1021/acs.jmedchem.5c03436