Chemo-Enzymatic Synthesis of Branched N-Acetyllactosamine Glycan Oligomers for Galectin-3 Inhibition

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F17%3A00483762" target="_blank" >RIV/61388971:_____/17:00483762 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1002/adsc.201700969" target="_blank" >http://dx.doi.org/10.1002/adsc.201700969</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/adsc.201700969" target="_blank" >10.1002/adsc.201700969</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Chemo-Enzymatic Synthesis of Branched N-Acetyllactosamine Glycan Oligomers for Galectin-3 Inhibition

Popis výsledku v původním jazyce

We present here a novel concept for the synthesis of branched N-acetyllactosamine (LacNAc) glycan structures. Through a combination of sequential enzymatic and chemical reactions of Leloir-glycosyltransferases, galactose oxidase and reductive amination, we obtained branched glycan oligomers with a variation of LacNAc and/or N',N ''-diacetyllactosamine (LacdiNAc) glycan epitopes. Incorporation of a branching point was accomplished by an optimized galactose oxidase protocol rendering the C-6 aldehyde functionality at the terminal galactose of a LacNAc oligomer. After glycan chain elongation by glycosyltransferases, the C-6 aldehyde-containing linear building block was conjugated with amine-linker functionalized glycans. Methanol and a temperature of 50 degrees C were found to be optimum conditions for the alpha-picoline borane-catalyzed reductive amination. Chemically branched glycans were obtained in high synthetic yields (approximate to 81%) in preparative batches. Product isolation was accomplished by preparative HPLC with good overall yields (>60%). The structural integrity was proven by ESI-MS and NMR. The herein synthesized branched LacNAc oligomers feature a variation of Lac(di)NAc epitopes and were confirmed to be potent inhibitors of human galectin-3 (Gal-3). The branched decasaccharide with two LacdiNAc-LacNAc branches ranks among the most potent poly-LacNAc-based Gal-3 inhibitors so far.

Název v anglickém jazyce

Chemo-Enzymatic Synthesis of Branched N-Acetyllactosamine Glycan Oligomers for Galectin-3 Inhibition

Popis výsledku anglicky

We present here a novel concept for the synthesis of branched N-acetyllactosamine (LacNAc) glycan structures. Through a combination of sequential enzymatic and chemical reactions of Leloir-glycosyltransferases, galactose oxidase and reductive amination, we obtained branched glycan oligomers with a variation of LacNAc and/or N',N ''-diacetyllactosamine (LacdiNAc) glycan epitopes. Incorporation of a branching point was accomplished by an optimized galactose oxidase protocol rendering the C-6 aldehyde functionality at the terminal galactose of a LacNAc oligomer. After glycan chain elongation by glycosyltransferases, the C-6 aldehyde-containing linear building block was conjugated with amine-linker functionalized glycans. Methanol and a temperature of 50 degrees C were found to be optimum conditions for the alpha-picoline borane-catalyzed reductive amination. Chemically branched glycans were obtained in high synthetic yields (approximate to 81%) in preparative batches. Product isolation was accomplished by preparative HPLC with good overall yields (>60%). The structural integrity was proven by ESI-MS and NMR. The herein synthesized branched LacNAc oligomers feature a variation of Lac(di)NAc epitopes and were confirmed to be potent inhibitors of human galectin-3 (Gal-3). The branched decasaccharide with two LacdiNAc-LacNAc branches ranks among the most potent poly-LacNAc-based Gal-3 inhibitors so far.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

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

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

Advanced Synthesis & Catalysis

ISSN

1615-4150

e-ISSN

—

Svazek periodika

359

Číslo periodika v rámci svazku

22

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

10

Strana od-do

4015-4024

Kód UT WoS článku

000416166300022

EID výsledku v databázi Scopus

2-s2.0-85034115972