We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Linear and cyclic oligo-β-(1 → 6)-D-glucosamines: Synthesis, conformations, and applications for design of a vaccine and oligodentate glycoconjugates.
- Authors
Gening, Marina L.; Tsvetkov, Yury E.; Titov, Denis V.; Gerbst, Alexey G.; Yudina, Olga N.; Grachev, Alexey A.; Shashkov, Alexander S.; Vidal, Sébastien; Imberty, Anne; Saha, Tanmoy; Kand, Dnyaneshwar; Talukdar, Pinaki; Pier, Gerald B.; Nifantiev, Nikolay E.
- Abstract
Poly-β-(1 → 6)-N-acetyl-D-glucosamine is an exopolysaccharide secreted by numerous pathogenic bacteria, including Staphylococcus aureus, Escherichia coli, Yersinia pestis, Bordetella pertussis, Acinetobacter baumannii, Burkholderia spp., and others. A convergent approach was developed for the synthesis of oligosaccharide fragments consisting of 5, 7, 9, and 11 glucosamine or N-acetylglucosamine units and for the preparation of five nona-β-(1 → 6)-D-glucosamines with various N-acetylation patterns. Penta- and nonaβ-(1 → 6)-D-glucosamines conjugated to protein carriers through a specially developed sulfhydryl linker proved to be highly immunogenic in mice and rabbits and elicited antibodies that mediated opsonic killing of multiple strains of S. aureus (including methicillin-resistant S. aureus, MRSA) and E. coli, and protected against S. aureus skin abscesses and lethal E. coli and B. cenocepacia peritonitis. These findings provide a basis for the construction of a unique semisynthetic vaccine against multiple bacterial targets. Conformational studies by means of special NMR experiments and computer modeling revealed that the oligo-β-(1 → 6)-D-glucosamine chain exists mostly in a helix-like conformation, where the terminal monosaccharides are arranged close to each other. Owing to this feature, oligoglucosamines consisting of 2 to 7 residues easily form products of cycloglycosylation. Cyclooligo-β-(1 → 6)-D-glucosamines represent a new family of functionalized cyclic oligosaccharides. Owing to their molecular architectonics, these compounds are convenient scaffolds for the design of conjugates with defined valency, symmetry, flexibility, and function.
- Subjects
GLUCOSAMINE synthase; GLYCOCONJUGATES; POLYSACCHARIDES; PATHOGENIC bacteria; STAPHYLOCOCCUS aureus; CARBOHYDRATES; SYNTHETIC vaccines
- Publication
Pure & Applied Chemistry, 2013, Vol 85, Issue 9, p1879
- ISSN
0033-4545
- Publication type
Article
- DOI
10.1351/PAC-CON-12-09-06