Streptococcus pneumoniae (SP) bacteria are one of the leading causes of bacterial infections in young children . Their capsular polysaccharides (CPS), whose chemical structure defines the different serotypes, are virulence factors. One of the most virulent SP serotype is the 19F. Its CPS structure is characterized by the trisaccharide repeating unit (→4)-β-D-ManpNAc-(1→4)-α-D-Glcp-(1→2)-α-L-Rhap-(1-OPO₃-→), with phosphodiester bridges connecting a residue of rhamnose at the reducing end of one unit to the N-acetylmannosamine at the non-reducing end of the adjacent one. Among the three monosaccharides, N-acetyl-β-D-mannosamine is supposed to be the immunodominant element. It has been demonstrated that there is an evident effect of the pneumococcal polysaccharide chain length on the immunogenicity . However, to elicit an immune response, a possible alternative to explore respect to the exposition of the long polysaccharide chain could be the multiple presentation of short fragments in a clusterized form, exploiting proper scaffolds. From this point of view, calixarenes have been shown to be versatile platforms for the preparation of multivalent glycoclusters . The possibility of subtly tuning size of the scaffold, valency and geometry of the epitope display, allowed to produce in the past efficient and selective calixarene based ligands, the glycocalixarenes, for carbohydrate recognition proteins . In this work we planned to exploit these macrocycles as scaffolds to design potential immunostimulants against 19F-SP serotype, linking to calixarenes multiple units of N-acetyl-β-D-mannosamine or of the 19F capsular trisaccharide repeating unit as saccharide epitope moieties (see Figure). The synthesis of the ligands with the achievement of structurally well-defined glycocalixarenes and their antigenic properties will be presented evidencing the effect of multivalency in increasing the ability of the single saccharide unit, when attached on the macrocycle, to compete with natural 19F CPS in the binding to specific anti-19F antibody.
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