Axial Symmetry Directs Ligand Orientation in Galectin-3
-rotational symmetry features of their saccharide cores, imposing direct control over their binding behavior. Using a combination of ligand-observed and protein-observed NMR spectroscopy, complemented by free energy calculations, we were able to comprehensively describe the symmetry-resolved binding poses within this ligand series as well as the underlying thermodynamics. Our work offers new strategies for designing galectin-3 inhibitors with predictable binding behavior and the delivery of substituents to defined locations within the binding pocket.
Authors
- Milan Kožíšek (ORCID: https://orcid.org/0000-0002-9476-3409)
- Radek Pohl (ORCID: https://orcid.org/0000-0001-7898-946X)
- Jan Choutka (ORCID: https://orcid.org/0000-0001-6290-9787)
- Kamil Parkan (ORCID: https://orcid.org/0000-0001-7585-6004)
- Jakub Zýka (ORCID: https://orcid.org/0000-0002-8944-6169)
- Nina Habanová (ORCID: https://orcid.org/0000-0001-6412-9901)
- Vít Prouza (ORCID: https://orcid.org/0000-0002-5976-5417)
- Martin Zavřel
- Jaroslav Kozák
- Pavel Srb
Institutions
- Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry (CZ)
- University of Chemistry and Technology, Prague (CZ)
Publication Details
- Journal
- Journal of Medicinal Chemistry
- Published
- 2026-07-26
- DOI
- https://doi.org/10.1021/acs.jmedchem.6c00031
- Primary Topic
- Galectins and Cancer Biology
- Type
- article
- Field-Weighted Citation Impact
- 0.00