Studies Towards the Synthesis of 6-Deoxy-heptopyranose Containing Campylobacter Glycans

  • Author / Creator
    Thota, V Narasimharao
  • Campylobacters are the leading cause of food-borne gastrointestinal illness worldwide. C. jejuni is the most commonly involved in human disease followed by C. coli. Although these infections usually resolve in a few days, they sometimes lead to the neurological auto-immune disorder, Guillain–Barré Syndrome. The cell surface of these pathogens is decorated by polysaccharides that contribute to virulence.
    The C. jejuni capsular polysaccharide (CPS) differentiates the 47 different serotypes identified to date. Although, currently there is no commercially-available vaccine against C. jejuni for humans, a CPS conjugate vaccine against C. jejuni 81-176 protects against diarrheal disease in non-human primates. Because of the large variety of serotypes, a practical vaccine must contain CPS from many different strains; however, the number required is not known.
    The structure of C. jejuni CPS varies widely from strain to strain and is often functionalized with a range of phase-variable modifications such as the addition of methyl, ethanolamine, aminoglycerol, and O-methyl phosphoramidate (MeOPN) groups. These CPSs possess a number of unusual structural motifs and prominent among these are the 6-deoxy-heptoses and the MeOPN group. The MeOPN phosphorus atom in these CPS is stereogenic and is found as a single stereoisomer.
    Although the CPS conjugate vaccine has 100% efficacy against diarrheal disease in animal models, a drawback to this vaccine is that it protects only against the 81-176 strain. The addition of serotypes from additional strains is necessary for better protection. However, the isolation of CPS in pure form from bacteria is difficult and the heterogeneity in the carbohydrate is not ideal for use in vaccines. Therefore, an alternate approach to access this material – synthetic chemistry – is necessary. Chemically synthesized CPSs will be well-defined and homogeneous, which can be used as antigens for vaccine development.
    This thesis was focused on the synthesis of CPS fragments from selected serotypes that contain 6-deoxy-heptopyranoses in the D-configuration. The synthesis of thioglycoside donors of 6-deoxy-D-heptopyranosides was focused in the first part. The second part of the thesis will focus on assembling the monosaccharide building blocks, including the 6-deoxy-D-heptopyranoside thioglycosides, into targeted CPS fragments.

  • Subjects / Keywords
  • Graduation date
    Spring 2020
  • Type of Item
  • Degree
    Doctor of Philosophy
  • DOI
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