497096-19-2Relevant academic research and scientific papers
Towards a synthetic glycoconjugate vaccine against Neisseria meningitidis A
Berkin, Ali,Coxon, Bruce,Pozsgay, Vince
, p. 4424 - 4433 (2007/10/03)
Albumin conjugates of synthetic fragments of the capsular polysaccharide of the Gram-negative bacterium Neisseria meningitidis serogroup A were prepared. The fragments include monosaccharides 1 [α-D-ManpNAc-(1 → 30)-(CH2)2NH2] and 2 [6-O-P(O)-(O-)2-α-D-ManpNAc-(1 → O)-(CH2)2N-H2], disaccharide 3 {α-D-ManpNAc[1 → O-P(O)(O-) → 6]-α-D-ManpNAc(1 → O)-(CH2)2NH2}, and trisaccharide 4 {α-D-ManpNAc-[1 → O-P(O)(O-) → 6]-α-D-ManpNAc-[1 → O-P(O)(O-) → 6]-α-D-ManpNAc-(1 → O)-(CH2)2NH2}. Two monosaccharide blocks were employed as key intermediates. The reducing-end mannose unit featured the NHAc group at C-2, and contained the aminoethyl spacer as the aglycon for the final bioconjugation. The interresidual phosphodiester linkages were fashioned from an anomerically positioned H-phosphonate group in a 2-azido-mannose building block. The spacer-linked saccharides 1-4 were N-acylated with hepta-4,6-dienoic acid and the resulting conjugated diene-equipped saccharides were subjected to Diels-Alder-type addition with maleimidobutyryl-group functionalized human serum albumin to form covalent conjugates containing up to 26 saccharide haptens per albumin molecule. Complete 1H, 13C, and 31P NMR assignments for 1-4 are given. Antigenicity of the neoglycoconjugates containing 1-4 was demonstrated by a double immunodiffusion assay which indicated that a fragment as small as a monosaccharide is recognized by a polyclonal meningococcus group A antiserum and that the O-acetyl group(s) present in the natural capsular material is not essential for antigenicity.
