title: Synthesis and preliminary biological evaluation of carba analogues from Neisseria meningitidis A capsular polysaccharide.
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.
authors.affiliation: Dipartimento di Chimica and ISTM-CNR, Università degli Studi di Milano, Italy.
authors.forename: Qi
authors.initials: Q
authors.lastname: Gao
authors.forename: Cristina
authors.initials: C
authors.lastname: Zaccaria
authors.forename: Marta
authors.initials: M
authors.lastname: Tontini
authors.forename: Laura
authors.initials: L
authors.lastname: Poletti
authors.forename: Paolo
authors.initials: P
authors.lastname: Costantino
authors.forename: Luigi
authors.initials: L
authors.lastname: Lay
mesh_terms: D000818:Animals; D054329:Carbasugars / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006595:Hexosamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D008585:Meningitis, Meningococcal / Q000517:prevention & control; D051379:Mice; D038381:Neisseria meningitidis, Serogroup A / Q000737:chemistry* / Q000276:immunology; D009844:Oligosaccharides / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology; D010710:Phosphates / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D044967:Serum / Q000276:immunology
chemical_list: D054329:Carbasugars; D006595:Hexosamines; D009844:Oligosaccharides; D010710:Phosphates; C002022:N-acetylmannosamine