Synthesis and unexpected binding of monofluorinated N,Nʹ-diacetylchitobiose and LacdiNAc to wheat germ agglutinin.

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F24%3A00585671" target="_blank" >RIV/61388971:_____/24:00585671 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/67985858:_____/24:00585671 RIV/61388963:_____/24:00585671 RIV/00216208:11310/24:10487994 RIV/60461373:22310/24:43928909 RIV/60461373:22330/24:43928909

Výsledek na webu

<a href="https://hdl.handle.net/11104/0353359" target="_blank" >https://hdl.handle.net/11104/0353359</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bioorg.2024.107395" target="_blank" >10.1016/j.bioorg.2024.107395</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Synthesis and unexpected binding of monofluorinated N,Nʹ-diacetylchitobiose and LacdiNAc to wheat germ agglutinin.

Popis výsledku v původním jazyce

Fluorination of carbohydrate ligands of lectins is a useful approach to examine their binding profile, improve their metabolic stability and lipophilicity, and convert them into 19F NMR-active probes. However, monofluorination of monovalent carbohydrate ligands often leads to a decreased or completely lost affinity. By chemical glycosylation, we synthesized the full series of methyl β-glycosides of N,N′-diacetylchitobiose (GlcNAcβ (1–4)GlcNAcβ1-OMe) and LacdiNAc (GalNAcβ(1–4)GlcNAcβ1-OMe) systematically monofluorinated at all hydroxyl positions. A competitive enzyme-linked lectin assay revealed that the fluorination at the 6′-position of chitobioside resulted in an unprecedented increase in affinity to wheat germ agglutinin (WGA) by one order of nmagnitude. For the first time, we have characterized the binding profile of a previously underexplored WGA ligand LacdiNAc. Surprisingly, 4′-fluoro-LacdiNAc bound WGA even stronger than unmodified LacdiNAc. These observations were interpreted using molecular dynamic calculations along with STD and transferred NOESY NMR techniques, which gave evidence for the strengthening of CH/π interactions after deoxyfluorination of the nside chain of the non-reducing GlcNAc. These results highlight the potential of fluorinated glycomimetics as highaffinity ligands of lectins and 19F NMR-active probe.

Název v anglickém jazyce

Synthesis and unexpected binding of monofluorinated N,Nʹ-diacetylchitobiose and LacdiNAc to wheat germ agglutinin.

Popis výsledku anglicky

Fluorination of carbohydrate ligands of lectins is a useful approach to examine their binding profile, improve their metabolic stability and lipophilicity, and convert them into 19F NMR-active probes. However, monofluorination of monovalent carbohydrate ligands often leads to a decreased or completely lost affinity. By chemical glycosylation, we synthesized the full series of methyl β-glycosides of N,N′-diacetylchitobiose (GlcNAcβ (1–4)GlcNAcβ1-OMe) and LacdiNAc (GalNAcβ(1–4)GlcNAcβ1-OMe) systematically monofluorinated at all hydroxyl positions. A competitive enzyme-linked lectin assay revealed that the fluorination at the 6′-position of chitobioside resulted in an unprecedented increase in affinity to wheat germ agglutinin (WGA) by one order of nmagnitude. For the first time, we have characterized the binding profile of a previously underexplored WGA ligand LacdiNAc. Surprisingly, 4′-fluoro-LacdiNAc bound WGA even stronger than unmodified LacdiNAc. These observations were interpreted using molecular dynamic calculations along with STD and transferred NOESY NMR techniques, which gave evidence for the strengthening of CH/π interactions after deoxyfluorination of the nside chain of the non-reducing GlcNAc. These results highlight the potential of fluorinated glycomimetics as highaffinity ligands of lectins and 19F NMR-active probe.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

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

Název periodika

Bioorganic Chemistry

ISSN

0045-2068

e-ISSN

1090-2120

Svazek periodika

147

Číslo periodika v rámci svazku

June 2024

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

12

Strana od-do

107395

Kód UT WoS článku

001238378800001

EID výsledku v databázi Scopus

2-s2.0-85192074801