Chemoenzymatic synthesis of α-dystroglycan core M1 O-mannose glycans

Zhang, Yan; Meng, Caicai; Jin, Lan; Chen, Xi; Wang, Fengshan; Cao, Hongzhi

doi:10.1039/c5cc02913a

Cited by 19 publications

(18 citation statements)

References 40 publications

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“…To acquire core structures 1 – 5 at gram scales for further enzymatic diversification, a concise chemical approach was designed using 2,6-diol 7 , a known monosaccharide imidate 14 8 , and a disaccharide imidate 15 9 as the key building blocks (Scheme 3). …”

Section: Chemical Synthesis Of Core Structures 1–5mentioning

confidence: 99%

Chemoenzymatic Assembly of Mammalian O‐Mannose Glycans

et al. 2018

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O-Mannose glycans, a family of highly heterogeneous complex glycans account up to 30% of total O-glycans in brain. Previous synthesis and functional studies only focused on the Core M3 O-mannose glycans of α-dystroglycan which are a causative factor for various muscular diseases. In this study, a highly efficient chemoenzymatic strategy was developed that enabled the first collective synthesis of 63 Core M1 and Core M2 O-mannose glycans. This chemoenzymatic strategy features the gram-scale chemical synthesis of 5 judiciously designed core structures, and the diversity-oriented modification of the core structures with 3 enzyme modules to provide 58 complex O-mannose glycans in a linear sequence that does not exceed 4 steps. Of note, 55 of these O-mannose glycans are synthesized for the first time. Using the printed O-mannose glycan array, the human brain protein CD33, a key factor in the modulation of Alzheimer’s disease was identified as strongly binding to sialylated Core M1 and Core M2.

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Section: Chemical Synthesis Of Core Structures 1–5mentioning

confidence: 99%

Chemoenzymatic Assembly of Mammalian O‐Mannose Glycans

et al. 2018

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“…39 Other examples have been shown for sequential OPME syntheses of Lewis x and sialyl LNnT pentasaccharides, 71 sialyl Lewis x hexasaccharide (Figure 7B), 71 and sialylated or fucosylated α-dystroglycan core M1 O-mannose glycans (Figure 7C). 72 …”

Section: Sequential Opme Processes For the Synthesis Of Extended Chaimentioning

confidence: 99%

One-pot multienzyme (OPME) systems for chemoenzymatic synthesis of carbohydrates

2016

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Glycosyltransferase-catalyzed enzymatic and chemoenzymatic syntheses are powerful approaches for the production of oligosaccharides, polysaccharides, glycoconjugates, and their derivatives. Enzymes involved in the biosynthesis of sugar nucleotide donors can be combined with the glycosyltransferases in one pot for efficient production of target glycans from simple monosaccharides and accpetors. The identification of enzymes involved in the salvage pathway of sugar nucleotide generation has greatly facilitate the development of simplified and efficient one-pot multienzyme (OPME) systems for synthesizing major glycan epitopes in mammalian glycomes. The applications of OPME methods are steadily gaining popularity mainly due to the increasing availability of wild-type and engineered enzymes. Substrate promiscuity of these enzymes and their mutants allows OPME synthesis of carbohydrates with naturally occurring post-glycosylational modificiation (PGMs) and their non-natural derivatives using modified monosaccharides as precursors. The OPME systems can be applied in sequential for synthesizing complex carbohydrates. The sequence of the sequential OPME processes, the glycosyltransferase used, and the substrate specificities of glycosyltransferasese define the structures of the products. The OPME and sequential OPME strategies can be extended to diverse glycans in other glycomes when suitable enzymes with substrate promiscuity become available. The Perspective summariezes the work of the authors and collaborators on the development of glycosyltransferase-based OPME systems for carbohydrate synthesis. Future directions are also discussed.

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“…Next, we turned our attention to enzymatic diversification of core structures 1-5 for the collective synthesis of core M1 and core M2 O-mannose glycans 16-71.P reviously,w e developed three enzyme modules to target three different glycosidic linkages presenting in branching structures II-VII (Scheme 1) for the synthesis of serine-appended core M1 Omannose glycans. [8] By taking advantage of the promiscuous substrate specificity of bacterial enzymes,weanticipated that these enzyme modules could also be applied for the synthesis of sterically hindered core M2 structures.A ss hown in Scheme 4a,e nzyme module 1i saone-pot three-enzyme system that was designed for b1-4-galactosylation to form the Galb1-4GlcNAc moiety. [10] Enzyme module 2isanother onepot three-enzyme system, which was designed for a2-3sialylation to form both Neu5Aca2-3Gal and Neu5Gca2-3Gal units.…”

Section: Angewandte Chemiementioning

confidence: 99%

“…To acquire core structures 1-5 at gram scales for further enzymatic diversification, ac oncise chemical approach was designed using 2,6-diol 7,k nown monosaccharide imidate 14, [8] and disaccharide imidate 15 [9] as the key building blocks (Scheme 3). It was envisaged that 2,6-diol 7 could serve as the only acceptor required for the synthesis of core structures 2-5 through regio-and stereoselective glycosylation (Scheme 3).…”

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confidence: 99%

“…[8] By taking advantage of the promiscuous substrate specificity of bacterial enzymes,weanticipated that these enzyme modules could also be applied for the synthesis of sterically hindered core M2 structures.A ss hown in Scheme 4a,e nzyme module 1i saone-pot three-enzyme system that was designed for b1-4-galactosylation to form the Galb1-4GlcNAc moiety. [8] By taking advantage of the promiscuous substrate specificity of bacterial enzymes,weanticipated that these enzyme modules could also be applied for the synthesis of sterically hindered core M2 structures.A ss hown in Scheme 4a,e nzyme module 1i saone-pot three-enzyme system that was designed for b1-4-galactosylation to form the Galb1-4GlcNAc moiety.…”

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