36th NARECOM - Lactose-Functionalized Carbosilane Glycodendrimers Are Highly Potent Multivalent Ligands for Galectin-9 Binding

The 36th NARECOM will take place on Wednesday, May 22nd, 2024 at 2:30 p.m. The specialist from the Institute of Experimental Medicine of the CAS, v. v. i., Ing. Monika Müllerová, Ph.D. , will introduce Lactose-Functionalized Carbosilane Glycodendrimers which are highly Potent Multivalent Ligands for Galectin-9 Binding. You are invited to visit this on-line seminar on https://cesnet.zoom.us/j/92333685068

ABSTRACT of the PRESENTATION

Lactose-Functionalized Carbosilane Glycodendrimers Are Highly Potent Multivalent Ligands for Galectin-9 Binding

Ing. Monika Müllerová, Ph.D.

Institute of Experimental Medicine of the CAS

 Galectins, a class of glycan-binding proteins, and their carbohydrate ligands are pivotal in modulating various biological functions. A profound comprehension of ligand-protein recognition mechanisms is imperative for advancements in galectin-targeted therapeutics1, 2. This research introduces a novel synthetic approach for lactose-functionalized carbosilane glycodendrimers (Lac-CS-DDMs) utilizing carbosilane dendrimers, the nanoscaffolds known for their minimal toxicity. Our findings highlight the exceptional affinity of these glycodendrimers, driven by dendritic effects, towards tandem-type galectins, with a notable preference for Gal-9. Quantitative analysis via enzyme-linked immunosorbent assay revealed that the third-generation dendritic ligand, equipped with 32 lactose units, exhibited a remarkable binding affinity to Gal-9 (IC50 = 970 nM), outperforming monovalent lactose by a factor of 1400. This underscores the transformative potential of multivalent presentations in enhancing ligand inhibitory effects. Additionally, through dynamic light scattering measurements, we established a correlation between the augmented affinity of glycodendrimer ligands for Gal-3, Gal-8, and particularly Gal-9, and the formation of consistent and stable galectin/Lac-CS-DDM aggregates.

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