Synthesis of <i>Campylobacter jejuni</i> capsular oligosaccharides and identification of a potential <i>O</i>-antigen against campylobacteriosis.

Abstract

The vaccines against campylobacteriosis are urgently needed because of the rising multidrug resistance of pathogenic <i>Campylobacter jejuni</i>. The capsular polysaccharides of these bacteria, containing unique 6-deoxy-β-d-<i>ido</i>-heptopyranosyl or l-<i>glycero</i>-β-d-<i>ido</i>-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 <i>C. jejuni</i> 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-<i>ido</i>-heptopyranosyl, α-d-idopyranosyl, and d-/l-<i>glycero</i>-α-d-<i>ido</i>-heptopyranosyl <i>ortho</i>-hexynylbenzoates as glycosylating agents under gold(I) catalysis. To demonstrate the versatility of these methods, concise synthesis of conjugatable <i>C. jejuni</i> capsular di-/tetra-/hexa-/octasaccharides, having a backbone of [→3)-6-deoxy-β-d-<i>ido</i>-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 <i>O</i>-antigen for developing vaccines against campylobacteriosis. This work should facilitate development of synthetic vaccines against <i>Campylobacter</i> infections.