Fucosyl glycosides for DC-SIGN targeting: Fucosylation strategies, synthesis and binding studies of model compounds

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22310%2F25%3A43931519" target="_blank" >RIV/60461373:22310/25:43931519 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60461373:22810/25:43931519

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0968089625001051" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0968089625001051</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bmc.2025.118164" target="_blank" >10.1016/j.bmc.2025.118164</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Fucosyl glycosides for DC-SIGN targeting: Fucosylation strategies, synthesis and binding studies of model compounds

Popis výsledku v původním jazyce

DC-SIGN, a C-type lectin receptor expressed on immune cells, is considered a promising target for immunomodulatory and antiviral therapies. While mannose-based glycomimetics have been extensively studied as DC- SIGN ligands, fucose-based strategies remain underexplored. This study explores the fucosylation of linear alcohols and sugars using eight different fucosyl donors, aiming at designing strategies for the development of fucose-based glycomimetics targeting DC-SIGN. Four types of leaving groups and two different acyl-based protecting groups on the donors were tested. The glycosylation of 3-azidopropan-1-ol exclusively yielded the (3-anomer, demonstrating high stereoselectivity. The azido group in the product is versatile, allowing for direct click chemistry reactions or reduction to an amine for further functionalization. Both types of reactions were demonstrated in a model reaction. In the glycosylation of a sugar, a disaccharide moiety of Lewis X antigen was selected as a target molecule. Only one of the eight tested fucosyl donors worked well in this reaction and provided the product in a reasonable yield. The disaccharide was also equipped with the 3-azidopropyl linker, facilitating future modifications. Finally, NMR studies confirmed compatibility of the linker with canonical Ca2+- dependent carbohydrate binding to DC-SIGN, suggesting potential for further development of fucose-based glycomimetics targeting this C-type lectin receptor.

Název v anglickém jazyce

Fucosyl glycosides for DC-SIGN targeting: Fucosylation strategies, synthesis and binding studies of model compounds

Popis výsledku anglicky

DC-SIGN, a C-type lectin receptor expressed on immune cells, is considered a promising target for immunomodulatory and antiviral therapies. While mannose-based glycomimetics have been extensively studied as DC- SIGN ligands, fucose-based strategies remain underexplored. This study explores the fucosylation of linear alcohols and sugars using eight different fucosyl donors, aiming at designing strategies for the development of fucose-based glycomimetics targeting DC-SIGN. Four types of leaving groups and two different acyl-based protecting groups on the donors were tested. The glycosylation of 3-azidopropan-1-ol exclusively yielded the (3-anomer, demonstrating high stereoselectivity. The azido group in the product is versatile, allowing for direct click chemistry reactions or reduction to an amine for further functionalization. Both types of reactions were demonstrated in a model reaction. In the glycosylation of a sugar, a disaccharide moiety of Lewis X antigen was selected as a target molecule. Only one of the eight tested fucosyl donors worked well in this reaction and provided the product in a reasonable yield. The disaccharide was also equipped with the 3-azidopropyl linker, facilitating future modifications. Finally, NMR studies confirmed compatibility of the linker with canonical Ca2+- dependent carbohydrate binding to DC-SIGN, suggesting potential for further development of fucose-based glycomimetics targeting this C-type lectin receptor.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

BIOORGANIC &amp; MEDICINAL CHEMISTRY

ISSN

0968-0896

e-ISSN

1464-3391

Svazek periodika

123

Číslo periodika v rámci svazku

1 June 2025

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

118164

Kód UT WoS článku

001457212600001

EID výsledku v databázi Scopus

2-s2.0-105000988336