The 2SO Skew‐Boat Conformation in <scp>L</scp>‐Iduronic Acid

Ochsenbein, Philippe; Bonin, Michel; Schenk‐Joß, Kurt; El-Hajji, Mohamed

doi:10.1002/anie.201105172

Cited by 16 publications

(14 citation statements)

References 27 publications

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“…This unambiguously demonstrates that the 2 S 0 skew‐boat geometry is necessary for the control of blood coagulation. The importance of the 2 S 0 conformer was further investigated by using NMR experiments, crystallography, and computational methods, ultimately resulting in the visualization of the 2 S 0 conformer by X‐ray diffraction …”

Section: Glycans Conformationmentioning

confidence: 99%

Conformational Studies of Oligosaccharides

Yang

Delbianco

2020

Chemistry A European J

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The conformation of am olecule strongly affects its function, as demonstrated for peptides and nucleic acids. This correlation is much less establishedf or carbohydrates, the most abundant organic materials in nature. Recent advances in synthetic and analytical techniques have enabled the study of carbohydrates at the molecular level. Recurrent structural features were identified as responsible for particular biological activities or materialp roperties. In this Minireview,r ecent achievements in the structuralc haracterization of carbohydrates, enabled by systematic studies of chemically defined oligosaccharides, are discussed. These findings can guide the development of more potent glycomimetics. Synthetic carbohydrate materials by design can be envisioned.

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Section: Glycans Conformationmentioning

confidence: 99%

Conformational Studies of Oligosaccharides

Yang

Delbianco

2020

Chemistry A European J

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“…It has been reported that L-iduronic acid can adopt 1 C 4 , 2 S 0 , and 4 C 1 conformations in glycosaminoglycans [31][32][33] and that this exibility is even a key feature of heparin. [34][35][36] In addition, Sattelle et al have calculated the free energy of L-iduronic acid and reported that (i) the ring can switch between conformations in microseconds, and (ii) 2-O-sulfation stabilizes the 1 C 4 conformation.…”

Section: Elucidating the Reason For Enhanced Enzymatic Conversionmentioning

confidence: 99%

A click-flipped enzyme substrate boosts the performance of the diagnostic screening for Hunter syndrome

et al. 2020

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“…It has been reported that l-iduronic acid can adopt 1 C 4 , 2 S 0 , and 4 C 1 conformations in glycosaminoglycans [31][32][33] and that this flexibility is even a key feature of heparin. [34][35][36] In addition, Sattelle et al have calculated the free energy of l-iduronic acid and reported that (i) the ring can switch between conformations in microseconds, and (ii) 2-O-sulfation stabilizes the 1 C 4 conformation.…”

Section: Elucidating the Reason For Enhanced Enzymatic Conversionmentioning

confidence: 99%

A Click-Flipped Enzyme Substrate Boosts the Performance of the Diagnostic Screening for Hunter Syndrome

Schwarz¹,

Skrinjar²,

Fink³

et al. 2020

Preprint

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We report on the unexpected finding that click modification of iduronyl azides results in a conformational flip of the pyranose ring, which led to the development of a new strategy for the design of superior enzyme substrates for the diagnostic assaying of iduronate-2-sulfatase (I2S), a lysosomal enzyme related to Hunter syndrome. Synthetic substrates are essential in testing newborns for metabolic disorders to enable early initiation of therapy. Our click-flipped iduronyl triazole showed a remarkably better performance with I2S than commonly used O-iduronates. We found that both O- and triazole-linked substrates are accepted by the enzyme, irrespective of their different conformations, but only the O-linked product inhibits the activity of I2S. Thus, in the long reaction times required for clinical assays, the triazole substrate substantially outperforms the O-iduronate. Applying our click-flipped substrate to assay I2S in dried blood spots sampled from affected patients and random newborns significantly increased the confidence in discriminating between these groups, clearly indicating the potential of the click-flip strategy to control the biomolecular function of carbohydrates.

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The ²S_O Skew‐Boat Conformation in L‐Iduronic Acid

Cited by 16 publications

References 27 publications

Conformational Studies of Oligosaccharides

Conformational Studies of Oligosaccharides

A click-flipped enzyme substrate boosts the performance of the diagnostic screening for Hunter syndrome

A Click-Flipped Enzyme Substrate Boosts the Performance of the Diagnostic Screening for Hunter Syndrome

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The 2SO Skew‐Boat Conformation in L‐Iduronic Acid

Cited by 16 publications

References 27 publications

Conformational Studies of Oligosaccharides

Conformational Studies of Oligosaccharides

A click-flipped enzyme substrate boosts the performance of the diagnostic screening for Hunter syndrome

A Click-Flipped Enzyme Substrate Boosts the Performance of the Diagnostic Screening for Hunter Syndrome

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Product

Resources

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The ²S_O Skew‐Boat Conformation in L‐Iduronic Acid