Advances in glycoside and oligosaccharide synthesis

Crawford, Conor J.; Seeberger, Peter H.

doi:10.1039/d3cs00321c

Cited by 30 publications

(15 citation statements)

References 443 publications

(682 reference statements)

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“…Enzymatic synthesis of complex glycans is a prime example of the latter area given the dearth of standardized and modular wet chemical synthetic approaches to these compounds. [ 203 ] Enantiomeric and stereoisomeric specificity are a big part of sugar/glycan chemistry because of their natural production by enzymes—so why try to compete with this? The examples above, including that of the O‐mannosyl glycan NeuNAcα2‐3Galβ1‐4GlcNAcβ1‐2Manα (N‐α) and cladribine highlight some possibilities in this area, [ 114 ] however, there are other applications where enzymatic synthesis of glycans can contribute.…”

Section: Discussionmentioning

confidence: 99%

Multienzymatic Cascades and Nanomaterial Scaffolding—A Potential Way Forward for the Efficient Biosynthesis of Novel Chemical Products

Hooe,

Smith,

Dean

et al. 2023

Advanced Materials

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Synthetic biology is touted as the next industrial revolution as it promises access to greener biocatalytic syntheses to replace many industrial organic chemistries. Here, it is shown to what synthetic biology can offer in the form of multienzyme cascades for the synthesis of the most basic of new materials—chemicals, including especially designer chemical products and their analogs. Since achieving this is predicated on dramatically expanding the chemical space that enzymes access, such chemistry will probably be undertaken in cell‐free or minimalist formats to overcome the inherent toxicity of non‐natural substrates to living cells. Laying out relevant aspects that need to be considered in the design of multi‐enzymatic cascades for these purposes is begun. Representative multienzymatic cascades are critically reviewed, which have been specifically developed for the synthesis of compounds that have either been made only by traditional organic synthesis along with those cascades utilized for novel compound syntheses. Lastly, an overview of strategies that look toward exploiting bio/nanomaterials for accessing channeling and other nanoscale materials phenomena in vitro to direct novel enzymatic biosynthesis and improve catalytic efficiency is provided. Finally, a perspective on what is needed for this field to develop in the short and long term is presented.

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Section: Discussionmentioning

confidence: 99%

Multienzymatic Cascades and Nanomaterial Scaffolding—A Potential Way Forward for the Efficient Biosynthesis of Novel Chemical Products

Hooe,

Smith,

Dean

et al. 2023

Advanced Materials

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“…[4] Yet, in practice, glycosylations are notoriously unreliable as properties of the reactants, such as stereochemistry, protecting group pattern, conformation, and leaving group, as well as the reaction conditions, including temperature, concentration, equivalents of activator, and residual water in the solvent influence the reactivity, selectivity, and efficiency of the reactions. [4,5] The effects of different factors concerning conditions and reactants on glycosylation selectivity and yield have been quantitated and among them, reaction temperature emerges as influential, [6][7][8] affecting both the rate of the desired reaction and the occurrence of undesired competing reactions. [9][10][11][12][13][14] Generally, it is accepted that glycosylations proceed rapidly within a relatively narrow temperature range.…”

Section: Introductionmentioning

confidence: 99%

Parametric Analysis of Donor Activation for Glycosylation Reactions

Lin,

Kuo,

Danglad‐Flores

et al. 2024

Chemistry A European J

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The chemical synthesis of complex oligosaccharides relies on efficient and highly reproducible glycosylation reactions. The outcome of a glycosylation is contingent upon several environmental factors, such as temperature, acidity, the presence of residual moisture, as well as the steric, electronic, and conformational aspects of the reactants. Each glycosylation proceeds rapidly and with a high yield within a rather narrow temperature range. For better control over glycosylations and to ensure fast and reliable reactions, a systematic analysis of 18 glycosyl donors revealed the effect of reagent concentration, water content, protecting groups, and structure of the glycosyl donors on the activation temperature. With these insights, we parametrize the first step of the glycosylation reaction to be executed reliably and efficiently.

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“…This heterogeneity encompasses complex monosaccharide compositions, sequences, linkage types, branching structures, and anomeric stereochemistry. 13,14 Consequently, research on glycans has lagged behind that on genes and proteins. It is worth noting that even minor differences in structural details, such as anomeric stereochemistry or glycosidic linkages, can profoundly impact biochemical processes involving glycans.…”

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confidence: 99%

“…However, this field still faces huge challenges, primarily arising from the low abundance and extensive structural heterogeneity of glycans. This heterogeneity encompasses complex monosaccharide compositions, sequences, linkage types, branching structures, and anomeric stereochemistry. , Consequently, research on glycans has lagged behind that on genes and proteins. It is worth noting that even minor differences in structural details, such as anomeric stereochemistry or glycosidic linkages, can profoundly impact biochemical processes involving glycans. , For instance, the blood groups H-trisaccharide (type IV) and A-trisaccharide are anomeric isomers.…”

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confidence: 99%

Precise Structural Analysis of Neutral Glycans Using Aerolysin Mutant T240R Nanopore

Lu,

Zhao,

et al. 2024

ACS Nano

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Glycans play vital roles in nearly all life processes of multicellular organisms, and understanding these activities is inseparable from elucidating the biological significance of glycans. However, glycan research has lagged behind that of DNA and protein due to the challenges posed by structural heterogeneity and isomerism (i.e., structures with equal molecular weights) the lack of high-efficiency structural analysis techniques. Nanopore technology has emerged as a sensitive single-molecule biosensor, shining a light on glycan analysis. However, a significant number of glycans are small and uncharged, making it challenging to elicit identifiable nanopore signals. Here we introduce a R-binaphthyl tag into glycans, which enhances the cation−π interaction between the derivatized glycan molecules and the nanopore interface, enabling the detection of neutral glycans with an aerolysin nanopore. This approach allows for the distinction of di-, tri-, and tetrasaccharides with monosaccharide resolution and has the potential for group discrimination, the monitoring of enzymatic transglycosylation reactions. Notably, the aerolysin mutant T240R achieves unambiguous identification of six disaccharide isomers, trisaccharide and tetrasaccharide linkage isomers. Molecular docking simulations reveal that multiple noncovalent interactions occur between residues R282, K238, and R240 and the glycans and R-binaphthyl tag, significantly slowing down their translocation across the nanopore. Importantly, we provide a demonstration of the kinetic translocation process of neutral glycan isomers, establishing a solid theoretical foundation for glycan nanopore analysis. The development of our technology could promote the analysis of glycan structural isomers and has the potential for nanopore-based glycan structural determination and sequencing.

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Advances in glycoside and oligosaccharide synthesis

Abstract: Here readers are introduced to the fundamental principles of glycoside bond formation and recent advances in glycoside and oligosaccharide synthesis.

Cited by 30 publications

References 443 publications

Multienzymatic Cascades and Nanomaterial Scaffolding—A Potential Way Forward for the Efficient Biosynthesis of Novel Chemical Products

Multienzymatic Cascades and Nanomaterial Scaffolding—A Potential Way Forward for the Efficient Biosynthesis of Novel Chemical Products

Parametric Analysis of Donor Activation for Glycosylation Reactions

Precise Structural Analysis of Neutral Glycans Using Aerolysin Mutant T240R Nanopore

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