Synthesis of C-linked neuraminic acid as potent immunogen for meningococcal meningitis and small cell lung cancer

CARB 83

Xuejun Yuan, yuanx@rpi.edu, Department of Chemistry, Rensselaer Polytechnic Institute, Troy, NY 12180 and Robert J. Linhardt, linhar@rpi.edu, Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY 12180.
Meningococcal meningitis is a severe childhood disease that often results in significant disability or death. The virulence of these organisms is attributable to structural mimicry between their common alpha(2,8)-polysialic acid (PSA) capsular polysaccharide and human tissue antigens, which allows the bacteria to evade immune surveillance. Currently, there is no effective vaccine to protect against the infection of Meningococcal meningitis. The glycosidic oxygen linkage in PSA represents an important target for modification in rational design of PSA based therapeutics. C-glycosides are resistant to degradation under physiological conditions. C-linked alpha(2,8) PSA oligomers are under construction through C-glycosylation under Barbier conditions in our lab. Major obstacles for preparation of glycosyl donor and acceptor have been overcome. Afterwards the C-analogs of PSA will be conjugated to immunogenic protein carriers to enhance their immunogenicity.