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Using NMR to Dissect the Chemical Space and O-Sulfation Effects within the O- and S-Glycoside Analogues of Heparan Sulfate
[Image: see text] 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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301708/ https://www.ncbi.nlm.nih.gov/pubmed/35874203 http://dx.doi.org/10.1021/acsomega.2c02070 |
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author | Meneghetti, Maria C.Z. Naughton, Lucy O’Shea, Conor Koffi Teki, Dindet S.-E. Chagnault, Vincent Nader, Helena B. Rudd, Timothy R. Yates, Edwin A. Kovensky, José Miller, Gavin J. Lima, Marcelo A. |
author_facet | Meneghetti, Maria C.Z. Naughton, Lucy O’Shea, Conor Koffi Teki, Dindet S.-E. Chagnault, Vincent Nader, Helena B. Rudd, Timothy R. Yates, Edwin A. Kovensky, José Miller, Gavin J. Lima, Marcelo A. |
author_sort | Meneghetti, Maria C.Z. |
collection | PubMed |
description | [Image: see text] 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. |
format | Online Article Text |
id | pubmed-9301708 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-93017082022-07-22 Using NMR to Dissect the Chemical Space and O-Sulfation Effects within the O- and S-Glycoside Analogues of Heparan Sulfate Meneghetti, Maria C.Z. Naughton, Lucy O’Shea, Conor Koffi Teki, Dindet S.-E. Chagnault, Vincent Nader, Helena B. Rudd, Timothy R. Yates, Edwin A. Kovensky, José Miller, Gavin J. Lima, Marcelo A. ACS Omega [Image: see text] 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. American Chemical Society 2022-07-08 /pmc/articles/PMC9301708/ /pubmed/35874203 http://dx.doi.org/10.1021/acsomega.2c02070 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Meneghetti, Maria C.Z. Naughton, Lucy O’Shea, Conor Koffi Teki, Dindet S.-E. Chagnault, Vincent Nader, Helena B. Rudd, Timothy R. Yates, Edwin A. Kovensky, José Miller, Gavin J. Lima, Marcelo A. Using NMR to Dissect the Chemical Space and O-Sulfation Effects within the O- and S-Glycoside Analogues of Heparan Sulfate |
title | Using NMR to Dissect
the Chemical Space and O-Sulfation Effects
within the O- and S-Glycoside
Analogues of Heparan Sulfate |
title_full | Using NMR to Dissect
the Chemical Space and O-Sulfation Effects
within the O- and S-Glycoside
Analogues of Heparan Sulfate |
title_fullStr | Using NMR to Dissect
the Chemical Space and O-Sulfation Effects
within the O- and S-Glycoside
Analogues of Heparan Sulfate |
title_full_unstemmed | Using NMR to Dissect
the Chemical Space and O-Sulfation Effects
within the O- and S-Glycoside
Analogues of Heparan Sulfate |
title_short | Using NMR to Dissect
the Chemical Space and O-Sulfation Effects
within the O- and S-Glycoside
Analogues of Heparan Sulfate |
title_sort | using nmr to dissect
the chemical space and o-sulfation effects
within the o- and s-glycoside
analogues of heparan sulfate |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301708/ https://www.ncbi.nlm.nih.gov/pubmed/35874203 http://dx.doi.org/10.1021/acsomega.2c02070 |
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