Illuminating glycoscience: synthetic strategies for FRET-enabled carbohydrate active enzyme probes

Singh, Meenakshi; Watkinson, Michael; Scanlan, Eoin M.; Miller, Gavin J.

doi:10.1039/d0cb00134a

Cited by 5 publications

(5 citation statements)

References 72 publications

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“…82,83 The images in Figure 3b illustrate how transfected Sandhoff fibroblasts with elevated HEX(NAG) activity exhibit an Increasing numbers of carbohydrate-based molecular probes are being developed as helpful tools for experimental glycobiology. 84,85 The immobilization of carbohydrate molecules within spatially defined microarrays enables rapid interrogation of complex biological samples and simultaneous identification of proteins such as lectins or antibodies with specific carbohydrate affinity. 86 Carbohydrate microarrays based on reactive probe molecules can be used to detect the presence of specific glycosidase activities.…”

Section: ■ Treatment Of Lysosomal Disordersmentioning

confidence: 99%

Advances in Optical Sensors of N-Acetyl-β-d-hexosaminidase (N-Acetyl-β-d-glucosaminidase)

Morsby

Smith

2022

Bioconjugate Chem.

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N-Acetyl-β-d-hexosaminidases (EC 3.2.1.52) are exo-acting glycosyl hydrolases that remove N-acetyl-β-d-glucosamine (Glc-NAc) or N-acetyl-β-d-galactosamine (Gal-NAc) from the nonreducing ends of various biomolecules including oligosaccharides, glycoproteins, and glycolipids. The same enzymes are sometimes called N-acetyl-β-d-glucosaminidases, and this review article employs the shorthand descriptor HEX(NAG) to indicate that the terms HEX or NAG are used interchangeably in the literature. The wide distribution of HEX(NAG) throughout the biosphere and its intracellular location in lysosomes combine to make it an important enzyme in food science, agriculture, cell biology, medical diagnostics, and chemotherapy. For more than 50 years, researchers have employed chromogenic derivatives of N-acetyl-β-d-glucosaminide in basic assays for biomedical research and clinical chemistry. Recent conceptual and synthetic innovations in molecular fluorescence sensors, along with concurrent technical improvements in instrumentation, have produced a growing number of new fluorescent imaging and diagnostics methods. A systematic summary of the recent advances in optical sensors for HEX(NAG) is provided under the following headings: assessing kidney health, detection and treatment of infectious disease, fluorescence imaging of cancer, treatment of lysosomal disorders, and reactive probes for chemical biology. The article concludes with some comments on likely future directions.

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Section: ■ Treatment Of Lysosomal Disordersmentioning

confidence: 99%

Advances in Optical Sensors of N-Acetyl-β-d-hexosaminidase (N-Acetyl-β-d-glucosaminidase)

Morsby

Smith

2022

Bioconjugate Chem.

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“…In this context, fluorescence imaging techniques have become powerful tools for the visualization of biomolecules, and the assessment of these phenomena. Such studies often require the derivatization of glycans by labeling with fluorophores 7 or by attachment to surfaces. 8 In this context, difluoroboron dipyrromethene (4,4-difluoro-4-bora-3a,4a-diaza- s -indacene) or BODIPY dyes, e.g.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, the sugar component provides enhanced solubility in polar solvents (including water), 21 biocompatibility, 22 targeting ability, 23 cell endocytosis, 24 and, in some instances, reduced toxicity 25 to the glyco-fluorophores. 7,8…”

Section: Introductionmentioning

confidence: 99%

Chemoselective reaction of methoxyaminomethyl BODIPYs with unprotected carbohydrates: a powerful tool for accessing BODIPY neoglycosides

Gómez,

García-Fernández,

Santana

et al. 2024

Org. Chem. Front.

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“…Access to, and analysis of, structurally homogeneous HS oligosaccharide sequences has developed significantly in recent years, − and the glycan toolbox of materials now available to deconvolute HS structural complexity is impressive. Such a toolbox, composed of chemically modified and synthetic HS saccharides, can be used to inform the HS structure-to-function effects at a molecular level. , Within this context, unnatural sequences such as those obtained from the replacement of glycosidic linkage oxygen with sulfur ( S -glycosides, Figure b) offer the exciting possibility of studying unique conformational preferences about the thioglycosidic and aglyconic bonds. − Subsequent comparison to native sequences will improve our understanding and capability to perturb HS structure-to-function relationships as well as access the untapped carbohydrate chemical space.…”

Section: Introductionmentioning

confidence: 99%

Using NMR to Dissect the Chemical Space and O-Sulfation Effects within the O- and S-Glycoside Analogues of Heparan Sulfate

et al. 2022

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Heparan sulfate (HS), a sulfated linear carbohydrate that decorates the cell surface and extracellular matrix, is ubiquitously distributed throughout the animal kingdom and represents a key regulator of biological processes and a largely untapped reservoir of potential therapeutic targets. The temporal and spatial variations in the HS structure underpin the concept of “heparanome” and a complex network of HS binding proteins. However, despite its widespread biological roles, the determination of direct structure-to-function correlations is impaired by HS chemical heterogeneity. Attempts to correlate substitution patterns (mostly at the level of sulfation) with a given biological activity have been made. Nonetheless, these do not generally consider higher-level conformational effects at the carbohydrate level. Here, the use of NMR chemical shift analysis, NOEs, and spin–spin coupling constants sheds new light on how different sulfation patterns affect the polysaccharide backbone geometry. Furthermore, the substitution of native O -glycosidic linkages to hydrolytically more stable S -glycosidic forms leads to observable conformational changes in model saccharides, suggesting that alternative chemical spaces can be accessed and explored using such mimetics. Employing a series of systematically modified heparin oligosaccharides (as a proxy for HS) and chemically synthesized O - and S -glycoside analogues, the chemical space occupied by such compounds is explored and described.

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Illuminating glycoscience: synthetic strategies for FRET-enabled carbohydrate active enzyme probes

Abstract: Carbohydrates are synthesised, refined and degraded by carbohydrate active enzymes. FRET is emerging as a powerful tool to monitor and quantify their activity as well as to test inhibitors as new drug candidates and monitor disease.

Cited by 5 publications

References 72 publications

Advances in Optical Sensors of N-Acetyl-β-d-hexosaminidase (N-Acetyl-β-d-glucosaminidase)

Advances in Optical Sensors of N-Acetyl-β-d-hexosaminidase (N-Acetyl-β-d-glucosaminidase)

Chemoselective reaction of methoxyaminomethyl BODIPYs with unprotected carbohydrates: a powerful tool for accessing BODIPY neoglycosides

Using NMR to Dissect the Chemical Space and O-Sulfation Effects within the O- and S-Glycoside Analogues of Heparan Sulfate

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