| dc.description.abstract | Zwitterionic polysaccharides (ZPSs), an emerging class of carbohydrate antigens with novel T-cell activation capability, have gained interest from the scientific community due to the role of cell surface glycans in pathogenesis. Advances in glycobiology have shown how glycan-protein molecular recognition processes play a role in the body’s adaptive immune response to pathogens. Contrary to nonspecific innate immune responses that prevent the spread of foreign pathogens throughout the body, the adaptive immune response mounts a pathogen-specific response by initiating the production and activation of T-cells and B-cells.
Zwitterionic glycan modifications, such as the incorporation of a phosphorous residue, govern host-pathogen interactions. Although it is recognized that this transformation play an important role to stimulate the host immune response, the purpose of phosphorous modifications on glycan remains unexplored in the literature. The inherent biological activity of ZPSs can be attributed to the three-dimensional structure of the polysaccharides with each repeating unit having a zwitterionic/alternating charge functionality in contrast to negative or neutral charge polysaccharides. Apart from the charge characteristic, the repeating units of these bacterial glycans are rich with highly immunodominant sugars like D-AAT (2-acetamido-4-amino-2,4,6-trideoxy-D-Galactosamine), D-GalNAc, D-Ribitol, and D-GlcNAc. Since the discoveries of ZPSs, various research groups around the world have taken up the challenging task of synthesizing these complex ZPSs, to acquire tools to study T-cell activation mechanism. Although these compounds’ biological activity is striking, it is truthfully their molecular structure that piqued our group’s interest as targets for total synthesis. Our group completed the first total syntheses of two zwitterionic repeating units, such as a 32-step synthesis of P. temperata and a 33-step synthesis P. vulgaris repeating units, both with alternating charges adjacent monosaccharides, which we believe is pertinent immunological activity. | |
