Synthesis of Asymmetric <i>N</i>-Glycans as Common Core Substrates for Structural Diversification through Selective Enzymatic Glycosylation

Pawar, Sujeet; Hsu, Li Jen; Reddy, Thatikonda Narendar; Ravinder, M.; Ren, Chien‐Tai; Lin, Yu‐Wei; Cheng, Yang‐Yu; Lin, Ting‐Yi; Hsu, Tsui-Ling; Wang, Shengkai; Wong, Chi‐Huey; Wu, Chung‐Yi

doi:10.1021/acschembio.0c00359

Cited by 14 publications

(6 citation statements)

References 56 publications

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“…Indeed, my own entry into the field involved adapting diastereoselective radical reactions to stereocontrolled 2-deoxy-β-glycoside synthesis. 3 With regard to more specific classes of glycans, the chemical synthesis of the N-glycans has advanced tremendously, 97,98 but is likely to be eclipsed by chemoenzymatic methods, particularly as a wider array of glycosyltransferases becomes available. 99 Automated oligosaccharide synthesis has reached a level at which preparation of linear glycans of previously unimaginable length can now be accomplished.…”

Section: ■ Crossroads 2: Stereocontrolled Glycan Synthesis As a Chall...mentioning

confidence: 99%

En Route to the Transformation of Glycoscience: A Chemist’s Perspective on Internal and External Crossroads in Glycochemistry

Crich

2020

J. Am. Chem. Soc.

101

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Carbohydrate chemistry is an essential component of the glycosciences and is fundamental to their progress. This Perspective takes the position that carbohydrate chemistry, or glycochemistry, has reached three crossroads on the path to the transformation of the glycosciences, and illustrates them with examples from the author's and other laboratories. The first of these potential inflexion points concerns the mechanism of the glycosylation reaction and the role of protecting groups. It is argued that the experimental evidence supports bimolecular S N 2-like mechanisms for typical glycosylation reactions over unimolecular ones involving stereoselective attack on naked glycosyl oxocarbenium ions. Similarly, it is argued that the experimental evidence does not support long-range stereodirecting participation of remote esters through bridged bicyclic dioxacarbenium ions in organic solution in the presence of typical counterions. Rational design and improvement of glycosylation reactions must take into account the roles of the counterion and of concentration. A second crossroads is that between mainstream organic chemistry and glycan synthesis. The case is made that the only real difference between glycan and organic synthesis is the formation of C−O rather than C−C bonds, with diastereocontrol, strategy, tactics, and elegance being of critical importance in both areas: mainstream organic chemists should feel comfortable taking this fork in the road, just as carbohydrate chemists should traveling in the opposite direction. A third crossroads is that between carbohydrate chemistry and medicinal chemistry, where there are equally many opportunities for traffic in either direction. The glycosciences have advanced enormously in the past decade or so, but creativity, input, and ingenuity of scientists from all fields is needed to address the many sophisticated challenges that remain, not the least of which is the development of a broader and more general array of stereospecific glycosylation reactions.

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Section: ■ Crossroads 2: Stereocontrolled Glycan Synthesis As a Chall...mentioning

confidence: 99%

En Route to the Transformation of Glycoscience: A Chemist’s Perspective on Internal and External Crossroads in Glycochemistry

Crich

2020

J. Am. Chem. Soc.

101

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“…25 Having an alternative source of asymmetric glycans would be of interest since they are difficult to synthesize and there is growing awareness of the biological implications of N-glycan asymmetry such as the complement-dependent cytotoxicity of monoclonal antibodies, 26 and influenza haemagglutinin binding. 27 Furthermore, asymmetric structures can be useful for the validation of mass spectrometry-based techniques. 28,29 Each of these examples is indicative of potential applications for these compounds.…”

Section: Introductionmentioning

confidence: 99%

Egg yolk sialylglycopeptide: purification, isolation and characterization of N-glycans from minor glycopeptide species

et al. 2022

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“…Tri and tetra-antennary complex N -glycans were synthesized in our laboratory. Details of the synthesis are provided in a previous study 40 . The NMR spectra and assignment of the N -glycans synthesized in our laboratory are illustrated in Supplementary Fig.…”

Section: Methodsmentioning

confidence: 99%

Structural identification of N-glycan isomers using logically derived sequence tandem mass spectrometry

et al. 2021

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N-linked glycosylation is one of the most important protein post-translational modifications. Despite the importance of N-glycans, the structural determination of N-glycan isomers remains challenging. Here we develop a mass spectrometry method, logically derived sequence tandem mass spectrometry (LODES/MSn), to determine the structures of N-glycan isomers that cannot be determined using conventional mass spectrometry. In LODES/MSn, the sequences of successive collision-induced dissociation are derived from carbohydrate dissociation mechanisms and apply to N-glycans in an ion trap for structural determination. We validate LODES/MSn using synthesized N-glycans and subsequently applied this method to N-glycans extracted from soybean, ovalbumin, and IgY. Our method does not require permethylation, reduction, and labeling of N-glycans, or the mass spectrum databases of oligosaccharides and N-glycan standards. Moreover, it can be applied to all types of N-glycans (high-mannose, hybrid, and complex), as well as the N-glycans degraded from larger N-glycans by any enzyme or acid hydrolysis.

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Synthesis of Asymmetric N-Glycans as Common Core Substrates for Structural Diversification through Selective Enzymatic Glycosylation

Cited by 14 publications

References 56 publications

En Route to the Transformation of Glycoscience: A Chemist’s Perspective on Internal and External Crossroads in Glycochemistry

En Route to the Transformation of Glycoscience: A Chemist’s Perspective on Internal and External Crossroads in Glycochemistry

Egg yolk sialylglycopeptide: purification, isolation and characterization of N-glycans from minor glycopeptide species

Structural identification of N-glycan isomers using logically derived sequence tandem mass spectrometry

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