Glycomimetic inhibitors of tandem-repeat galectins: Simple and efficient
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F24%3A00585278" target="_blank" >RIV/61388971:_____/24:00585278 - isvavai.cz</a>
Alternative codes found
RIV/68407700:21460/24:00373340 RIV/00216208:11310/24:10479581
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S0045206824001366?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0045206824001366?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.bioorg.2024.107231" target="_blank" >10.1016/j.bioorg.2024.107231</a>
Alternative languages
Result language
angličtina
Original language name
Glycomimetic inhibitors of tandem-repeat galectins: Simple and efficient
Original language description
The binding of human galectins by glycomimetic inhibitors is a promising therapeutic approach. The structurally distinct group of tandem-repeat galectins has scarcely been studied so far, and there is hardly any knowledge on their ligand specificity or their inhibitory potential, particularly concerning non-natural carbohydrates. Here, we present the synthesis of a library of seven 3-O-disubstituted thiodigalactoside-derived glycomimetics and their affinity to two tandem-repeat galectins, Gal-8 and Gal-9. The straightforward synthesis of these glycomimetics involved dibutyltin oxide-catalyzed 3,3-O-disubstitution of commercially available unprotected thiodigalactoside, and conjugation of various aryl substituents by copper-catalyzed Huisgen azide-alkyne cycloaddition (CuAAC). The inhibitory potential of the prepared glycomimetics for Gal-8 and Gal-9 was assessed, and compared with the established galectins Gal-1 and Gal-3. The introduction of C-3 substituents resulted in an over 40-fold increase in affinity compared with unmodified TDG. The structure-affinity relations within the studied series were discussed using molecular modeling. Furthermore, the prepared glycomimetics were shown to scavenge Gal-8 and Gal-9 from the surface of cancer cells. This pioneering study on the synthetic inhibitors especially of Gal-9 identified lead compounds that may be used in further biomedical research.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
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
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Bioorganic Chemistry
ISSN
0045-2068
e-ISSN
1090-2120
Volume of the periodical
145
Issue of the periodical within the volume
April 24
Country of publishing house
NL - THE KINGDOM OF THE NETHERLANDS
Number of pages
13
Pages from-to
107231
UT code for WoS article
001197668500001
EID of the result in the Scopus database
2-s2.0-85186065776