MCZ Meneghetti
Using NMR to Dissect the Chemical Space and O-Sulfation Effects within the O- and S-Glycoside Analogues of Heparan Sulfate.
Meneghetti, MCZ; Naughton, L; O'Shea, C; Koffi Teki, DS-E; Chagnault, V; Nader, HB; Rudd, TR; Yates, EA; Kovensky, J; Miller, Gavin; Andrade De Lima, Marcelo
Authors
L Naughton
C O'Shea
DS-E Koffi Teki
V Chagnault
HB Nader
TR Rudd
EA Yates
J Kovensky
Gavin Miller g.j.miller@keele.ac.uk
Marcelo Andrade De Lima m.andrade.de.lima@keele.ac.uk
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.
Journal Article Type | Article |
---|---|
Acceptance Date | Jun 28, 2022 |
Online Publication Date | Jul 8, 2022 |
Publication Date | Jul 19, 2022 |
Publicly Available Date | Mar 28, 2024 |
Journal | ACS Omega |
Electronic ISSN | 2470-1343 |
Publisher | American Chemical Society |
Peer Reviewed | Peer Reviewed |
Volume | 7 |
Issue | 28 |
Pages | 24461 - 24467 |
DOI | https://doi.org/10.1021/acsomega.2c02070 |
Publisher URL | https://pubs.acs.org/doi/10.1021/acsomega.2c02070 |
Files
O- and S-glycosides_R3_final.docx
(1.2 Mb)
Document
Publisher Licence URL
https://creativecommons.org/licenses/by-nc-nd/4.0/
acsomega.2c02070.pdf
(3.4 Mb)
PDF
Publisher Licence URL
https://creativecommons.org/licenses/by-nc-nd/4.0/
You might also like
Preparation of a 4′‐Thiouridine Building‐Block for Solid‐Phase Oligonucleotide Synthesis
(2023)
Journal Article
Fluorinated nucleosides, nucleotides and sugar nucleotides
(2023)
Journal Article
Downloadable Citations
About Keele Repository
Administrator e-mail: research.openaccess@keele.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2024
Advanced Search