The Gram-negative encapsulated bacterium Neisseria meningitidis type A (MenA) is a major cause of meningitis in developing countries, especially in the sub-Saharan region of Africa. The development and manufacture of an efficient glycoconjugate vaccine against MenA is greatly hampered by the poor hydrolytic stability of its capsular polysaccharide, consisting of (1→6)-linked 2-acetamido-2-deoxy--D-mannopyranosyl phosphate repeating units. The replacement of the ring oxygen with a methylene group to get a carbocyclic analogue leads to the loss of the acetalic character of the phosphodiester and consequently to the enhancement of its chemical stability. Here we report the synthesis of oligomers (mono-, di- and trisaccharide) of carba-N-acetylmannosamine-1-O-phosphate as candidates for stabilized analogues of the corresponding fragments of MenA capsular polysaccharide. Each of the synthesized compounds contains a phosphodiester-linked aminopropyl spacer at its reducing end to allow for protein conjugation. The inhibition abilities of the synthetic molecules were investigated by a competitive ELISA assay, showing that only the carba-disaccharide is recognized by a polyclonal anti-MenA serum with an affinity similar to a native MenA oligosaccharide with average polymerization degree 3.
Synthesis and Preliminary Biological Evaluation of Carba Analogues from Neisseria meningitidis A Capsular Polysaccharide / Q. Gao, C. Zaccaria, M. Tontini, L. Poletti, P. Costantino, L. Lay. - In: ORGANIC & BIOMOLECULAR CHEMISTRY. - ISSN 1477-0520. - 10:33(2012), pp. 6673-6681.
|Titolo:||Synthesis and Preliminary Biological Evaluation of Carba Analogues from Neisseria meningitidis A Capsular Polysaccharide|
GAO, QI (Primo)
ZACCARIA, CRISTINA (Secondo)
LAY, LUIGI (Ultimo)
|Parole Chiave:||PROTEIN CONJUGATE VACCINES ; GROUP-A ; GOLD NANOPARTICLES ; ANTIGENS ; PREVENTION; PROTECTION ; SEROGROUPS|
|Settore Scientifico Disciplinare:||Settore CHIM/06 - Chimica Organica|
|Data di pubblicazione:||2012|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1039/C2OB25222H|
|Appare nelle tipologie:||01 - Articolo su periodico|