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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Meneghetti, Maria CZ, Naughton, Lucy, O'Shea, Conor, Teki, Dindet SE Koffi, Chagnault, Vincent, Nader, Helena B, Rudd, Timothy R ORCID: 0000-0003-4434-0333, Yates, Edwin A ORCID: 0000-0001-9365-5433, Kovensky, Jose, Miller, Gavin J et al (show 1 more authors) and Lima, Marcelo A (2022) Using NMR to Dissect the Chemical Space and O-Sulfation Effects within the O- and S-Glycoside Analogues of Heparan Sulfate. ACS OMEGA, 7 (28). pp. 24461-24467.

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Using NMR to Dissect the Chemical Space and iOi-Sulfation Effects within the iOi- and iSi-Glycoside Analogues of Heparan Sul.pdf - Published version
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Official URL: http://dx.doi.org/10.1021/acsomega.2c02070

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.

Item Type:	Article
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	17 Oct 2022 15:50
Last Modified:	18 Oct 2023 07:45
DOI:	10.1021/acsomega.2c02070
Open Access URL:	https://doi.org/10.1021/acsomega.2c02070
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3165562