Galectins (Gal), proteins that bind carbohydrate ligands of glycans, represent a fundamental regulatory system that modulates many biological processes. Advances in Gal-targeted therapy must be based on a detailed understanding of ligand and protein recognition mechanisms. For glycodendrimer-based multivalent ligands (glyco-DDMs), the so-called multivalent enhancement effect is known, where the resulting affinity of the multivalent system can be up to an order of magnitude higher than the simple sum of the affinities of the monovalent ligands. In our publication, we have presented a synthetic procedure for preparing a series of glyco-DDMs with lactose ligands. We observed the selective affinity, for tandem-type galectins (Gal-8 and Gal-9). Quantitative analysis (ELISA) revealed that our third-generation dendrimeric ligand with 32 sugar units has 1400 times higher affinity for Gal-9 than monovalent lactose, surpassing the nanomolar limit (IC50 = 970 nM). In addition, using DLS particle size studies, we also demonstrated a link between the affinity of glycodendrimers for galectins and the aggregation behavior of such complexes. Since abnormal expression of galectins is associated with many pathological processes, including cancer, the findings published in this work may contribute to new therapeutic strategies. The publication will appear in Biomacromolecules at the end of August 2023.
- Müllerová, M.; Hovorková, M.; Závodná, T.; Červenková Št́astná, L.; Krupková, A.; Hamala, V.; Nováková, K.; Topinka, J.; Bojarová, P.*; Strašák, T.* Lactose-Functionalized Carbosilane Glycodendrimers Are Highly Potent Multivalent Ligands for Galectin-9 Binding: Increased Glycan Affinity to Galectins Correlates with Aggregation Behavior. Biomacromolecules 2023. https://doi.org/10.1021/acs.biomac.3c00426.