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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F23%3A00575346" target="_blank" >RIV/61388963:_____/23:00575346 - isvavai.cz</a>

Alternative codes found

RIV/61388971:_____/23:00575346 RIV/67985858:_____/23:00575346 RIV/68378041:_____/23:00575346 RIV/00216208:11310/23:10471499

Result on the web

<a href="https://pubs.acs.org/doi/10.1021/acs.biomac.3c00426" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.biomac.3c00426</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.biomac.3c00426" target="_blank" >10.1021/acs.biomac.3c00426</a>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2023

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Biomacromolecules

ISSN

1525-7797

e-ISSN

1526-4602

Volume of the periodical

24

Issue of the periodical within the volume

11

Country of publishing house

US - UNITED STATES

Number of pages

13

Pages from-to

4705-4717

UT code for WoS article

001065419100001

EID of the result in the Scopus database

2-s2.0-85172905862