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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
Author(s) -
Calloni Ilaria,
Unione Luca,
JiménezOsés Gonzalo,
Corzana Francisco,
Del Bino Linda,
Corrado Alessio,
Pitirollo Olimpia,
Colombo Cinzia,
Lay Luigi,
Adamo Roberto,
JiménezBarbero Jesús
Publication year - 2018
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201801003
Subject(s) - neisseria meningitidis , chemistry , context (archaeology) , moiety , polysaccharide , monomer , methylene , stereochemistry , molecule , bacteria , biochemistry , organic chemistry , biology , polymer , paleontology , genetics
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phosphorylated monomer have been analyzed and compared to those of its carba‐analogue, where the endocyclic oxygen has been replaced by a methylene moiety.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.