Synthesis of Campylobacter jejuni capsular oligosaccharides and identification of a potential O-antigen against campylobacteriosis

Abstract

The vaccines against campylobacteriosis are urgently needed because of the rising multidrug resistance of pathogenic Campylobacter jejuni. The capsular polysaccharides of these bacteria, containing unique 6-deoxy-β-d-ido-heptopyranosyl or l-glycero-β-d-ido-heptopyranosyl residues, have emerged as attractive antigens. Expeditious assembly of the oligosaccharides derived from these glycans is challenging because β-d-idopyranosidic linkages are formidable to directly construct. Furthermore, whether the synthetic C. jejuni oligosaccharides could induce sufficient immunogenicity as the potential antigens remains unexplored. Here, we report a protocol for directly forming β-d-idopyranosidic bonds using α-d-6-deoxy-ido-heptopyranosyl, α-d-idopyranosyl, and d-/l-glycero-α-d-ido-heptopyranosyl ortho-hexynylbenzoates as glycosylating agents under gold(I) catalysis. To demonstrate the versatility of these methods, concise synthesis of conjugatable C. jejuni capsular di-/tetra-/hexa-/octasaccharides, having a backbone of [→3)-6-deoxy-β-d-ido-heptopyranosyl-(1→4)-2-acetamido-2-deoxy-β-d-glucopyranosyl-(1→], has been achieved. The immunogenicity assessment of the glycoconjugates, prepared by conjugating the synthesized oligosaccharides to cross-reactive material 197, reveals the disaccharide as a potential O-antigen for developing vaccines against campylobacteriosis. This work should facilitate development of synthetic vaccines against Campylobacter infections.