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The Conformation of the Mannopyranosyl Phosphate Repeating Unit of the Capsular Polysaccharide of Neisseria meningitidis Serogroup A and Its Carba‐Mimetic
Neisseria meningitidis serogroup A (MenA) is an aerobic diplococcal Gram‐negative bacterium responsible for epidemic meningitis disease. Its capsular polysaccharide (CPS) has been identified as the primary virulence factor of MenA. This polysaccharide suffers from chemical lability in water. Thus, t...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6220853/ https://www.ncbi.nlm.nih.gov/pubmed/30443159 http://dx.doi.org/10.1002/ejoc.201801003 |
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author | Calloni, Ilaria Unione, Luca Jiménez‐Osés, Gonzalo Corzana, Francisco Del Bino, Linda Corrado, Alessio Pitirollo, Olimpia Colombo, Cinzia Lay, Luigi Adamo, Roberto Jiménez‐Barbero, Jesús |
author_facet | Calloni, Ilaria Unione, Luca Jiménez‐Osés, Gonzalo Corzana, Francisco Del Bino, Linda Corrado, Alessio Pitirollo, Olimpia Colombo, Cinzia Lay, Luigi Adamo, Roberto Jiménez‐Barbero, Jesús |
author_sort | Calloni, Ilaria |
collection | PubMed |
description | Neisseria meningitidis serogroup A (MenA) is an aerobic diplococcal Gram‐negative bacterium responsible for epidemic meningitis disease. Its capsular polysaccharide (CPS) has been identified as the primary virulence factor of MenA. This polysaccharide suffers from chemical lability in water. Thus, the design and synthesis of novel and hydrolytically stable structural analogues of MenA CPS may provide additional tools for the development of therapies against this disease. In this context, the structural features of the natural phosphorylated monomer have been analyzed and compared to those of its carba‐analogue, where the endocyclic oxygen has been replaced by a methylene moiety. The lowest energy geometries of the different molecules have been calculated using a combination of quantum mechanical techniques and molecular dynamics simulations. The predicted results have been compared and validated using NMR experiments. The results indicate that the more stable designed glycomimetics may adopt the conformation adopted by the natural monomer, although they display a wider flexibility around the torsional degrees of freedom. |
format | Online Article Text |
id | pubmed-6220853 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-62208532018-11-13 The Conformation of the Mannopyranosyl Phosphate Repeating Unit of the Capsular Polysaccharide of Neisseria meningitidis Serogroup A and Its Carba‐Mimetic Calloni, Ilaria Unione, Luca Jiménez‐Osés, Gonzalo Corzana, Francisco Del Bino, Linda Corrado, Alessio Pitirollo, Olimpia Colombo, Cinzia Lay, Luigi Adamo, Roberto Jiménez‐Barbero, Jesús European J Org Chem Full Papers Neisseria meningitidis serogroup A (MenA) is an aerobic diplococcal Gram‐negative bacterium responsible for epidemic meningitis disease. Its capsular polysaccharide (CPS) has been identified as the primary virulence factor of MenA. This polysaccharide suffers from chemical lability in water. Thus, the design and synthesis of novel and hydrolytically stable structural analogues of MenA CPS may provide additional tools for the development of therapies against this disease. In this context, the structural features of the natural phosphorylated monomer have been analyzed and compared to those of its carba‐analogue, where the endocyclic oxygen has been replaced by a methylene moiety. The lowest energy geometries of the different molecules have been calculated using a combination of quantum mechanical techniques and molecular dynamics simulations. The predicted results have been compared and validated using NMR experiments. The results indicate that the more stable designed glycomimetics may adopt the conformation adopted by the natural monomer, although they display a wider flexibility around the torsional degrees of freedom. John Wiley and Sons Inc. 2018-08-17 2018-09-09 /pmc/articles/PMC6220853/ /pubmed/30443159 http://dx.doi.org/10.1002/ejoc.201801003 Text en © 2018 The Authors. Published by Wiley‐VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Full Papers Calloni, Ilaria Unione, Luca Jiménez‐Osés, Gonzalo Corzana, Francisco Del Bino, Linda Corrado, Alessio Pitirollo, Olimpia Colombo, Cinzia Lay, Luigi Adamo, Roberto Jiménez‐Barbero, Jesús The Conformation of the Mannopyranosyl Phosphate Repeating Unit of the Capsular Polysaccharide of Neisseria meningitidis Serogroup A and Its Carba‐Mimetic |
title | The Conformation of the Mannopyranosyl Phosphate Repeating Unit of the Capsular Polysaccharide of Neisseria meningitidis Serogroup A and Its Carba‐Mimetic |
title_full | The Conformation of the Mannopyranosyl Phosphate Repeating Unit of the Capsular Polysaccharide of Neisseria meningitidis Serogroup A and Its Carba‐Mimetic |
title_fullStr | The Conformation of the Mannopyranosyl Phosphate Repeating Unit of the Capsular Polysaccharide of Neisseria meningitidis Serogroup A and Its Carba‐Mimetic |
title_full_unstemmed | The Conformation of the Mannopyranosyl Phosphate Repeating Unit of the Capsular Polysaccharide of Neisseria meningitidis Serogroup A and Its Carba‐Mimetic |
title_short | The Conformation of the Mannopyranosyl Phosphate Repeating Unit of the Capsular Polysaccharide of Neisseria meningitidis Serogroup A and Its Carba‐Mimetic |
title_sort | conformation of the mannopyranosyl phosphate repeating unit of the capsular polysaccharide of neisseria meningitidis serogroup a and its carba‐mimetic |
topic | Full Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6220853/ https://www.ncbi.nlm.nih.gov/pubmed/30443159 http://dx.doi.org/10.1002/ejoc.201801003 |
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