Exploring calixarene-based clusters for efficient functional presentation of Streptococcus pneumoniae saccharides

[Display omitted] •A mobile calix[6]arene for the clustered presentation of Streptoccoccus pneumoniae 19F capsular polysaccharide fragments.•The calix[6]arene glycocluster efficiently binds to anti-19F antibodies.•A step forward towards the use of calixarenes as carriers for the development of fully synthetic antibacterial vaccines. Calixarenes are promising scaffolds for an efficient clustered exposition of multiple saccharide antigenic units. Herein we report the synthesis and biological evaluation of a calix[6]arene functionalized with six copies of the trisaccharide repeating unit of Streptococcus pneumoniae (SP) serotype 19F. This system has demonstrated its ability to efficiently inhibit the binding between the native 19F capsular polysaccharide and anti-19F antibodies, despite a low number of exposed saccharide antigens, well mimicking the epitope presentations in the polysaccharide. The calix[6]arene mobile scaffold has been selected for functionalization with SP 19F repeating unit after a preliminary screening of four model glycocalixarenes, functionalized with N-acetyl mannosamine, and differing in the valency and/or conformational properties. This work is a step forward towards the development of new fully synthetic calixarenes comprising small carbohydrate antigens as potential carbohydrate-based vaccine scaffolds.