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• W4284972519 endingPage "24467" @default.
• W4284972519 startingPage "24461" @default.
• W4284972519 abstract "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." @default.
• W4284972519 created "2022-07-10" @default.
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• W4284972519 date "2022-07-08" @default.
• W4284972519 modified "2023-10-14" @default.
• W4284972519 title "Using NMR to Dissect the Chemical Space and <i>O</i>-Sulfation Effects within the <i>O</i>- and <i>S</i>-Glycoside Analogues of Heparan Sulfate" @default.
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• W4284972519 doi "https://doi.org/10.1021/acsomega.2c02070" @default.
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• W4284972519 hasPublicationYear "2022" @default.
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