Chemo-Enzymatic Synthesis of Branched N-Acetyllactosamine Glycan Oligomers for Galectin-3 Inhibition
The result's identifiers
Result code in 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>
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
Chemo-Enzymatic Synthesis of Branched N-Acetyllactosamine Glycan Oligomers for Galectin-3 Inhibition
Original language description
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.
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
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Advanced Synthesis & Catalysis
ISSN
1615-4150
e-ISSN
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Volume of the periodical
359
Issue of the periodical within the volume
22
Country of publishing house
DE - GERMANY
Number of pages
10
Pages from-to
4015-4024
UT code for WoS article
000416166300022
EID of the result in the Scopus database
2-s2.0-85034115972