Lactose-Functionalized Carbosilane Glycodendrimers Are Highly Potent Multivalent Ligands for Galectin-9 Binding: Increased Glycan Affinity to Galectins Correlates with Aggregation Behavior.

Müllerová, Monika; Hovorková, Michaela; Závodná, Táňa; Červenková Šťastná, Lucie; Krupková, Alena; Hamala, Vojtěch; Nováková, Kateřina; Topinka, Jan; Bojarová, Pavla; Strašák, Tomáš

doi:https://dx.doi.org/10.1021/acs.biomac.3c00426

Number of the records: 1

Lactose-Functionalized Carbosilane Glycodendrimers Are Highly Potent Multivalent Ligands for Galectin-9 Binding: Increased Glycan Affinity to Galectins Correlates with Aggregation Behavior.

1.

SYSNO ASEP	0575346
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Lactose-Functionalized Carbosilane Glycodendrimers Are Highly Potent Multivalent Ligands for Galectin-9 Binding: Increased Glycan Affinity to Galectins Correlates with Aggregation Behavior.
Author(s)	Müllerová, Monika (UCHP-M)_{RID, ORCID, SAI} Hovorková, Michaela (MBU-M) Závodná, Táňa (UEM-P) Červenková Šťastná, Lucie (UCHP-M)_{RID, ORCID, SAI} Krupková, Alena (UCHP-M)_{RID, ORCID, SAI} Hamala, Vojtěch (UCHP-M)_{RID, SAI, ORCID} Nováková, Kateřina (UOCHB-X)_{RID, ORCID} Topinka, Jan (UEM-P)_{RID, ORCID} Bojarová, Pavla (MBU-M)_ORCID Strašák, Tomáš (UCHP-M)_{RID, ORCID, SAI}
Source Title	Biomacromolecules. - : American Chemical Society - ISSN 1525-7797 Roč. 24, č. 11 (2023), s. 4705-4717
Number of pages	13 s.
Language	eng - English
Country	US - United States
Keywords	polysaccharides ; carbosilanes ; glycodendrimers
OECD category	Organic chemistry
R&D Projects	LTC19049 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	GA23-05146S GA ČR - Czech Science Foundation (CSF)
	LM2018124 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	EF16_013/0001821 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
Method of publishing	Open access
Institutional support	UCHP-M - RVO:67985858 ; MBU-M - RVO:61388971 ; UEM-P - RVO:68378041 ; UOCHB-X - RVO:61388963
UT WOS	001065419100001
EID SCOPUS	85172905862
DOI	10.1021/acs.biomac.3c00426
Annotation	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.
Workplace	Institute of Chemical Process Fundamentals
Contact	Eva Jirsová, jirsova@icpf.cas.cz, Tel.: 220 390 227
Year of Publishing	2024
Electronic address	https://pubs.acs.org/doi/10.1021/acs.biomac.3c00426

Number of the records: 1