Using NMR to Dissect the Chemical Space and O-Sulfation Effects within the O- and S-Glycoside Analogues of Heparan Sulfate. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue ACS Omega Année : 2022

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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1
Maria C. Z. Meneghetti
  • Fonction : Auteur
Lucy Naughton
  • Fonction : Auteur
Conor O'Shea
  • Fonction : Auteur
Dindet S.-E. Koffi Teki
Helena B. Nader
  • Fonction : Auteur
Timothy R. Rudd
  • Fonction : Auteur
Edwin A. Yates
  • Fonction : Auteur
Gavin J. Miller
  • Fonction : Auteur
Marcelo A. Lima
  • Fonction : Auteur

Résumé

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.

Domaines

Chimie

Dates et versions

hal-03740512 , version 1 (29-07-2022)

Identifiants

Citer

Maria C. Z. Meneghetti, Lucy Naughton, Conor O'Shea, Dindet S.-E. Koffi Teki, Vincent Chagnault, et al.. Using NMR to Dissect the Chemical Space and O-Sulfation Effects within the O- and S-Glycoside Analogues of Heparan Sulfate.. ACS Omega, 2022, 7 (28), pp.24461--24467. ⟨10.1021/acsomega.2c02070⟩. ⟨hal-03740512⟩
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