Top‐Down Chemoenzymatic Approach to a High‐Mannose‐Type Glycan Library: Synthesis of a Common Precursor and Its Enzymatic Trimming

Koizumi, Akihiko; Matsuo, Ichiro; Takatani, Maki; Seko, Akira; Hachisu, Mitsugu; Takeda, Yoichi; Ito, Yukishige

doi:10.1002/ange.201301613

Cited by 19 publications

(17 citation statements)

References 59 publications

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“…Having the designed tridecasaccharide in our hands, its fluorophoric modification was conducted in order to facilitate the screening of the enzymatic reactions and the analysis of glycan-protein interactions, essentially as reported previously. [18] Thus, the tridecasaccharide 59 was first treated with an aqueous solution of NH 4 HCO 3 [22] to give the corresponding glycosylamine 77, which was immediately reacted with fluorenyl- Figure 2. Overview of the chemo-enzymatic synthesis of high-mannose-type glycans.…”

Section: Resultsmentioning

confidence: 99%

“…methoxycarbonyl (Fmoc)-glycine pentafluorophenyl ester (Fmoc-Gly-OPfp) in DMSO at freezing temperature to produce compound 78. [18,23] Deprotection of the Fmoc group (79) and treatment with the succinimide ester of BODIPY-FL gave the fluorescently labeled tridecasaccharide 1.…”

Section: Resultsmentioning

confidence: 99%

“…Taking these circumstances into consideration, we were led to design a non-natural-type glycan as a common precursor, which was to be converted to a variety of high-mannose-type glycans by enzymatic digestion. As the first generation approach, we have reported the non-natural tetradecasaccharide I as a common precursor, whose non-reducing ends were capped by Glc, Gal, and GlcNAc, in order to achieve selective trimming of the A-, B-, and C-arm in an orthogonal manner [18] (Figure 2 a). In fact, digestion with logically defined sets of glycosidases gave a variety of high-mannose-type glycans.…”

Section: Introductionmentioning

confidence: 99%

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Construction of a High‐Mannose‐Type Glycan Library by a Renewed Top‐Down Chemo‐Enzymatic Approach

Fujikawa

Koizumi

Hachisu

et al. 2015

Chemistry A European J

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A comprehensive method for the construction of a high-mannose-type glycan library by systematic chemo-enzymatic trimming of a single Man9-based precursor was developed. It consists of the chemical synthesis of a non-natural tridecasaccharide precursor, the orthogonal demasking of the non-reducing ends, and trimming by glycosidases, which enabled a comprehensive synthesis of high-mannose-type glycans in their mono- or non-glucosylated forms. It employed glucose, isopropylidene, and N-acetylglucosamine groups for blocking the A-, B-, and C-arms, respectively. After systematic trimming of the precursor, thirty-seven high-mannose-type glycans were obtained. The power of the methodology was demonstrated by the enzymatic activity of human recombinant N-acetylglucosaminyltransferase-I toward M7-M3 glycans, clarifying the substrate specificity in the context of high-mannose-type glycans.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Construction of a High‐Mannose‐Type Glycan Library by a Renewed Top‐Down Chemo‐Enzymatic Approach

Fujikawa

Koizumi

Hachisu

et al. 2015

Chemistry A European J

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“…Under these circumstances, we decided to explore an approach employing a non‐natural type of glycan as a common precursor, which was to be converted into a variety of high‐mannose‐type glycans by enzymatic digestion. As a first‐generation approach, we designed the tetradecasaccharide common precursor I , whose non‐reducing ends were capped by d ‐glucose (Glc), d ‐galactose (Gal), and N ‐acetyl‐ d ‐glucosamine (GlcNAc), in order to achieve selective trimming of its A‐, B‐, and C‐arms in an orthogonal manner (Figure a) …”

Section: Chemoenzymatic Synthesis Of High‐mannose‐type Oligosaccharidesmentioning

confidence: 99%

“…For the synthesis of the B‐arm part, the glycosylation of mannosyl donor 11 bearing a pentafluoropropionyl (PFP) group at O‐4 and mannosyl acceptor 12 was activated with MeOTf to afford disaccharide 13 (Scheme ). The PFP group was removed and the hydroxyl group thus generated in 14 was reacted with the Gal donor 15 , producing the trisaccharide 16 .…”

Section: Chemoenzymatic Synthesis Of High‐mannose‐type Oligosaccharidesmentioning

confidence: 99%

Approaches toward High-Mannose-Type Glycan Libraries

Fujikawa

Seko

Takeda

et al. 2015

The Chemical Record

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Asparagine-linked (N-linked) sugar chains are widely found in the rough endoplasmic reticulum (ER), which has attracted renewed attention because of its participation in the glycoprotein quality control process. In the ER, newly formed glycoproteins are properly folded to higher-order structures by the action of a variety of lectin chaperones and processing enzymes and are transported into the Golgi, while terminally misfolded glycoproteins are carried into the cytosol for degradation. A group of proteins related to this system are known to recognize subtle differences in the high-mannose-type oligosaccharide structures of glycoproteins; however, their molecular foundations are still unclear. In order to gain a more precise understanding, our group has established a strategy for the systematic synthesis of high-mannose-type glycans. More recently, we have developed "top-down" chemoenzymatic approaches that allow expeditious access to theoretically all types of high-mannose glycans. This strategy comprehensively delivered 37 high-mannose-type glycans, including G1M9-M3 glycans, and opened up the possibility of the elucidation of structure-function relationships with a series of high-mannose-type glycans.

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Synthesis of Fucosylated Chondroitin Sulfate Nonasaccharide as a Novel Anticoagulant Targeting Intrinsic Factor Xase Complex

et al. 2018

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Fucosylated chondroitin sulfate (FuCS) is a structurally distinct glycosaminoglycan, and its oligosaccharides exhibit excellent anticoagulant activity with lower risks of adverse effects and bleeding. Herein we report a facile approach to the synthesis of FuCS hexa‐ and nonasaccharides on the basis of the enzymatic degradation of chondroitin over 12 linear steps. As compared with a clinical low‐molecular‐weight heparin drug (enoxaparin), the nonasaccharide synthesized in this study displayed similar APTT activity and selective intrinsic factor Xase complex inhibitory activity ((12.9±0.83) nm) by binding to factor IXa with high affinity, thus offering promise for the development of new anticoagulant agents targeting the intrinsic coagulation pathway.

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Top‐Down Chemoenzymatic Approach to a High‐Mannose‐Type Glycan Library: Synthesis of a Common Precursor and Its Enzymatic Trimming

Cited by 19 publications

References 59 publications

Construction of a High‐Mannose‐Type Glycan Library by a Renewed Top‐Down Chemo‐Enzymatic Approach

Construction of a High‐Mannose‐Type Glycan Library by a Renewed Top‐Down Chemo‐Enzymatic Approach

Approaches toward High-Mannose-Type Glycan Libraries

Synthesis of Fucosylated Chondroitin Sulfate Nonasaccharide as a Novel Anticoagulant Targeting Intrinsic Factor Xase Complex

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