Reverse thiophosphorylase activity of a glycoside phosphorylase in the synthesis of an unnatural Manβ1,4GlcNAc library
This journal is © The Royal Society of Chemistry..
β-Mannosides are ubiquitous in nature, with diverse roles in many biological processes. Notably, Manβ1,4GlcNAc a constituent of the core N-glycan in eukaryotes was recently identified as an immune activator, highlighting its potential for use in immunotherapy. Despite their biological significance, the synthesis of β-mannosidic linkages remains one of the major challenges in glycoscience. Here we present a chemoenzymatic strategy that affords a series of novel unnatural Manβ1,4GlcNAc analogues using the β-1,4-d-mannosyl-N-acetyl-d-glucosamine phosphorylase, BT1033. We show that the presence of fluorine in the GlcNAc acceptor facilitates the formation of longer β-mannan-like glycans. We also pioneer a "reverse thiophosphorylase" enzymatic activity, favouring the synthesis of longer glycans by catalysing the formation of a phosphorolysis-stable thioglycoside linkage, an approach that may be generally applicable to other phosphorylases.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Chemical science - 14(2023), 42 vom: 01. Nov., Seite 11638-11646 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Keenan, Tessa [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Revised 03.04.2024 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1039/d3sc04169g |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a This journal is © The Royal Society of Chemistry. | ||
| 520 | |a β-Mannosides are ubiquitous in nature, with diverse roles in many biological processes. Notably, Manβ1,4GlcNAc a constituent of the core N-glycan in eukaryotes was recently identified as an immune activator, highlighting its potential for use in immunotherapy. Despite their biological significance, the synthesis of β-mannosidic linkages remains one of the major challenges in glycoscience. Here we present a chemoenzymatic strategy that affords a series of novel unnatural Manβ1,4GlcNAc analogues using the β-1,4-d-mannosyl-N-acetyl-d-glucosamine phosphorylase, BT1033. We show that the presence of fluorine in the GlcNAc acceptor facilitates the formation of longer β-mannan-like glycans. We also pioneer a "reverse thiophosphorylase" enzymatic activity, favouring the synthesis of longer glycans by catalysing the formation of a phosphorolysis-stable thioglycoside linkage, an approach that may be generally applicable to other phosphorylases | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Porter, Jack |e verfasserin |4 aut | |
| 700 | 1 | |a Vendeville, Jean-Baptiste |e verfasserin |4 aut | |
| 700 | 1 | |a Wheatley, David E |e verfasserin |4 aut | |
| 700 | 1 | |a Ghirardello, Mattia |e verfasserin |4 aut | |
| 700 | 1 | |a Wahart, Alice J C |e verfasserin |4 aut | |
| 700 | 1 | |a Ahmadipour, Sanaz |e verfasserin |4 aut | |
| 700 | 1 | |a Walton, Julia |e verfasserin |4 aut | |
| 700 | 1 | |a Galan, M Carmen |e verfasserin |4 aut | |
| 700 | 1 | |a Linclau, Bruno |e verfasserin |4 aut | |
| 700 | 1 | |a Miller, Gavin J |e verfasserin |4 aut | |
| 700 | 1 | |a Fascione, Martin A |e verfasserin |4 aut | |
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