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Lactose-Functionalized Carbosilane Glycodendrimers Are Highly Potent Multivalent Ligands for Galectin-9 Binding: Increased Glycan Affinity to Galectins Correlates with Aggregation Behavior.
- 1.0575346 - ÚCHP 2024 RIV US eng J - Článek v odborném periodiku
Müllerová, Monika - Hovorková, Michaela - Závodná, Táňa - Červenková Šťastná, Lucie - Krupková, Alena - Hamala, Vojtěch - Nováková, Kateřina - Topinka, Jan - Bojarová, Pavla - Strašák, Tomáš
Lactose-Functionalized Carbosilane Glycodendrimers Are Highly Potent Multivalent Ligands for Galectin-9 Binding: Increased Glycan Affinity to Galectins Correlates with Aggregation Behavior.
Biomacromolecules. Roč. 24, č. 11 (2023), s. 4705-4717. ISSN 1525-7797. E-ISSN 1526-4602
Grant CEP: GA MŠMT(CZ) LTC19049; GA ČR(CZ) GA23-05146S; GA MŠMT(CZ) LM2018124; GA MŠMT(CZ) EF16_013/0001821
Institucionální podpora: RVO:67985858 ; RVO:61388971 ; RVO:68378041 ; RVO:61388963
Klíčová slova: polysaccharides * carbosilanes * glycodendrimers
Obor OECD: Organic chemistry; Biochemistry and molecular biology (UOCHB-X); Biochemistry and molecular biology (MBU-M); Bioproducts (products that are manufactured using biological material as feedstock) biomaterials, bioplastics, biofuels, bioderived bulk and fine chemicals, bio-derived novel materials (UEM-P)
Impakt faktor: 6.2, rok: 2022
Způsob publikování: Open access
https://pubs.acs.org/doi/10.1021/acs.biomac.3c00426
Galectins, the glycan binding proteins, and their respective carbohydrate ligands represent a unique fundamental regulatory network modulating a plethora of biological processes. The advances in galectin-targeted therapy must be based on a deep understanding of the mechanism of ligand−protein recognition. Carbosilane dendrimers, the well-defined and finely tunable nanoscaffolds with low toxicity, are promising for multivalent carbohydrate ligand presentation to target galectin receptors. The study discloses a synthetic method for two types of lactose functionalized carbosilane glycodendrimers (Lac-CS-DDMs). Furthermore, we report their outstanding, dendritic effect-driven affinity to tandem-type galectins, especially Gal-9. In the enzyme linked immunosorbent assay, the affinity of the third-generation multivalent dendritic ligand bearing 32 lactose units to Gal-9 reached nanomolar values (IC50 = 970 nM), being a 1400-fold more effective inhibitor than monovalent lactose for this protein. This demonstrates a game-changing impact of multivalent presentation on the inhibitory effect of a ligand as simple as lactose. Moreover, using DLS hydrodynamic diameter measurements, we correlated the increased affinity of the glycodendrimer ligands to Gal-3 and Gal-8 but especially to Gal-9 with the formation of relatively uniform and stable galectin/Lac-CS-DDM aggregates.
Trvalý link: https://hdl.handle.net/11104/0345132
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