Polyvalent C-glycomimetics based on L-fucose or D-mannose as potent DC-SIGN antagonists

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F17%3A00475989" target="_blank" >RIV/61388963:_____/17:00475989 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60461373:22330/17:43913113 RIV/60461373:22810/17:43913113

Výsledek na webu

<a href="http://dx.doi.org/10.1039/c7ob00322f" target="_blank" >http://dx.doi.org/10.1039/c7ob00322f</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/c7ob00322f" target="_blank" >10.1039/c7ob00322f</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Polyvalent C-glycomimetics based on L-fucose or D-mannose as potent DC-SIGN antagonists

Popis výsledku v původním jazyce

The C-type lectin DC-SIGN expressed on immature dendritic cells is a promising target for antiviral drug development. Previously, we have demonstrated that mono- and divalent C-glycosides based on n-manno and t-fuco configurations are promising DC-SIGN ligands. Here, we described the convergent synthesis of C-glycoside dendrimers decorated with 4, 6, 9, and 12 alpha-L-fucopyranosyl units and with 9 and 12 alpha-D-mannopyranosyl units. Their affinity against DC-SIGN was assessed by surface plasmon resonance (SPR) assays. For comparison, parent 0-glycosidic dendrimers were synthesized and tested, as well. A clear increase of both affinity and multivalency effect was observed for C-glycomimetics of both types (mannose and fucose). However, when dodecavalent C-glycosidic dendrimers were compared, there was no difference in affinity regarding the sugar unit (L-fuco, IC50 17 mu M, u-manno, IC50 12 pM). For the rest of glycodendrimers with L-fucose or u-mannose attached by the O- or C-glycosidic linkage, C-glycosidic dendrimers were significantly more active. These results show that in addition to the expected physiological stability, the biological activity of C-glycoside mimetics is higher in comparison to the corresponding O-glycosides and therefore these glycomimetic multivalent systems represent potentially promising candidates for targeting DC-SIGN.

Název v anglickém jazyce

Polyvalent C-glycomimetics based on L-fucose or D-mannose as potent DC-SIGN antagonists

Popis výsledku anglicky

The C-type lectin DC-SIGN expressed on immature dendritic cells is a promising target for antiviral drug development. Previously, we have demonstrated that mono- and divalent C-glycosides based on n-manno and t-fuco configurations are promising DC-SIGN ligands. Here, we described the convergent synthesis of C-glycoside dendrimers decorated with 4, 6, 9, and 12 alpha-L-fucopyranosyl units and with 9 and 12 alpha-D-mannopyranosyl units. Their affinity against DC-SIGN was assessed by surface plasmon resonance (SPR) assays. For comparison, parent 0-glycosidic dendrimers were synthesized and tested, as well. A clear increase of both affinity and multivalency effect was observed for C-glycomimetics of both types (mannose and fucose). However, when dodecavalent C-glycosidic dendrimers were compared, there was no difference in affinity regarding the sugar unit (L-fuco, IC50 17 mu M, u-manno, IC50 12 pM). For the rest of glycodendrimers with L-fucose or u-mannose attached by the O- or C-glycosidic linkage, C-glycosidic dendrimers were significantly more active. These results show that in addition to the expected physiological stability, the biological activity of C-glycoside mimetics is higher in comparison to the corresponding O-glycosides and therefore these glycomimetic multivalent systems represent potentially promising candidates for targeting DC-SIGN.

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

2017

Kód důvěrnosti údajů

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

Název periodika

Organic & Biomolecular Chemistry

ISSN

1477-0520

e-ISSN

—

Svazek periodika

15

Číslo periodika v rámci svazku

18

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

10

Strana od-do

3995-4004

Kód UT WoS článku

000401147200025

EID výsledku v databázi Scopus

2-s2.0-85021647583