A highly convergent and efficient strategy was developed for the chemical synthesis of complex oligosaccharides of Streptococcus pneumoniae type 3 capsular polysaccharides that contain multiple glucuronic acid units. Once the oligoglucosides were efficiently and stereoselectively assembled, the designated glucose units were regioselectively oxidized to glucuronic acid in one step at the final synthetic stage, which helped avoid difficult glycosylations that involved glucuronic acid. The target oligosaccharides had a free amino group at the reducing terminus and varied caps at the non-reducing terminus to enable further modification and structure-activity relationship studies. Immunological evaluations of the oligosaccharide-tetanus toxoid conjugates showed that they elicited robust T-cell-dependent immunoglobulin G antibody responses and that the sugar chain length had a major impact on their immunological properties. In particular, the penta- and hexasaccharides were identified as promising antigens for vaccine development.
Oligosaccharides, immunology, glycoconjugates, vaccines, glycosylation, glycoengineering
Publication DOI: 10.1002/chem.201800754Journal NLM ID: 9513783Publisher: Weinheim: VCH Verlagsgesellschaft/Verlag I
Correspondence: zguo@chem.ufl.edu; guofenggu@sdu.edu.cn
Institutions: National Glycoengineering Research Center Shandong Provincial Key Laboratory of Carbohydrate Chemistry and Glycobiology Shandong University 27 Shanda Nan Lu, Jinan 250100, China, Department of Chemistry, University of Florida 214 Leigh Hall, Gainesville, FL, USA
Methods: 13C NMR, 1H NMR, TLC, ELISA, chemical synthesis, chemical methods, MALDI-TOF MS, glycosylation, optical rotation measurement, immunological assays, conjugation
Found