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Bioinformatics Resources for the Study of Glycan-Mediated Protein Interactions
Published on: January 20, 2022
Axial Symmetry Directs Ligand Orientation in Galectin-3
Nina Habanová1,2, Jakub Zýka3, Vít Prouza3
1Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo náměstí 542/2, 160 00 Prague, Czech Republic.
Journal of Medicinal Chemistry
|July 27, 2026
Summary
Molecular symmetry controls how small molecules bind to galectin-3, a key target in drug design. This research offers new strategies for creating predictable galectin-3 inhibitors.
Area of Science:
- Medicinal Chemistry
- Structural Biology
- Biophysics
Background:
- Controlling ligand orientation in binding sites is crucial for drug design but remains challenging.
- Lectin-carbohydrate interactions, like those involving galectin-3, are highly specific.
- Lack of universal design principles hinders predictable ligand binding control.
Purpose of the Study:
- To demonstrate how molecular symmetry can control small molecule binding to galectin-3.
- To explore the use of C2-rotational symmetry in designing galectin-3 ligands.
- To provide strategies for predictable galectin-3 inhibitor design.
Main Methods:
- Synthesis of galectin-3 ligands with varying C2-rotational symmetry.
- Ligand-observed and protein-observed NMR spectroscopy.
- Free energy calculations to analyze binding thermodynamics and poses.
Main Results:
- Successfully controlled galectin-3 ligand binding using molecular symmetry.
- Comprehensive description of symmetry-resolved binding poses and thermodynamics.
- Demonstrated predictable binding behavior based on ligand symmetry.
Conclusions:
- Molecular symmetry is a viable strategy for controlling ligand binding to galectin-3.
- This approach enables precise delivery of substituents to specific binding pocket locations.
- Offers new avenues for developing targeted galectin-3 inhibitors.
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