A saccharide fragment related to Streptococcus Pneumoniae 19F serotype for the preparation of glyconanoplatforms

Glyconanomaterials (GNMs) have recently emerged as promising drug delivery systems; by displaying functional carbohydrate groups on their surfaces, they serve as drug carriers and possess effective adjuvant or targeting properties, therefore significantly improving drug uptake [1]. The rise in Antibiotic Microbial Resistance (AMR), coupled with the slow development of new antibiotics, has created a global health crisis. Vaccination is one of the most efficient methods for preventing infections, although developing safe and effective vaccines with broad protection against infectious diseases remains a major challenge. GNMs can be exploited as vaccine delivery systems, by encapsulating an antigen inside the nanoparticle itself or attaching it to its surface. Sugar-coated nanomaterials have a high density of carbohydrates on their surface and can mimic the natural arrangement of carbohydrates on cell surfaces through multivalent presentation. In addition, GNMs offer the possibility to display simultaneously different ligands, i.e. bacterial saccharide antigens and dendritic cells targeting agents, leading to the design of new glycoplatforms for immune system activation. In this regard, we selected a capsular bacterium, namely S. Pneumoniae 19F, as a model, because it is very representative of the situation, given its association with AMR and its inherent virulence. Capsular bacteria present a wide polysaccharide cover on their surface, which has been demonstrated to serve as a critical virulence factor. In particular, the aim of this work has been the synthesis of the SP19F trisaccharide epitope (Tris19F) functionalized with a PEG-N3 group on its reducing end, which can be exploited to link the antigen to a GNM system via a click chemistry reaction.