Synthesis and biological evaluation of a trisaccharide repeating unit derivative of streptococcus pneumoniae 19A capsular polysaccharide

Streptococcus pneumoniae (SP) is a common human pathogen associated with a broad spectrum of disease and it is still a leading cause of mortality and morbidity worldwide [1]. Nowadays the most effective strategy to reduce the burden of disease caused by SP is vaccination. Administered vaccines contain fragments of bacterial capsular polysaccharide (CP), which are important surface antigens of these invading bacteria. New research strategies in this field aim at developing nanomaterials loaded with carbohydrate antigens, which are emerging as synthetic vaccine candidates [2,3]. The prerequisite of this approach is the identification of the shortest polysaccharide fragment able to be recognized by the natural antibody and to be immunogenic. In this framework has emerged our interest in SP 19A serotype, which is one of the serotype responsible for the bulk of pneumococcal disease [4]. In particular, we aim at developing a derivative of the SP19A repeating unit, -D-ManpNAc-(14)--D-Glcp-(13)-Rhap-(1-O-phosphate), still endowed with biological activity and suitable for conjugation to different nanomaterials. Herein we will describe the synthesis of compound 1, the saccharide portion of SP 19A repeating unit conjugated at the reducing end to an aminopropyl linker. This compound has been obtained through a glycosylation reaction between a properly protected thiophenyl -D-ManpNAc-(14)--D-Glcp disaccharide and a new suitable -amino propyl rhamnoside acceptor. Classical competitive Elisa assay demonstrated that compound 1 has inhibitory properties and is recognized by the anti-19A antibody.