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Issue 33, 2012
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Synthesis and preliminary biological evaluation of carba analogues from Neisseria meningitidis A capsular polysaccharide

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Abstract

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-α-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 of 3.

Graphical abstract: Synthesis and preliminary biological evaluation of carba analogues from Neisseria meningitidis A capsular polysaccharide

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Supplementary files

Article information


Submitted
30 Jan 2012
Accepted
11 Jun 2012
First published
13 Jun 2012

Org. Biomol. Chem., 2012,10, 6673-6681
Article type
Paper

Synthesis and preliminary biological evaluation of carba analogues from Neisseria meningitidis A capsular polysaccharide

Q. Gao, C. Zaccaria, M. Tontini, L. Poletti, P. Costantino and L. Lay, Org. Biomol. Chem., 2012, 10, 6673
DOI: 10.1039/C2OB25222H

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