Synthesis, Self-assembly and Langerin Recognition Studies of a Resorcinarene-based Glycocluster Exposing a Hyaluronic Acid Thiodisaccharide Mimetic

CRISTÓFALO, ALEJANDRO EZEQUIEL; NIETO, PEDRO M; THEPAUT, MICHEL; FIESCHI, FRANCK; DI CHENNA, PABLO HÉCTOR HECTOR; UHRIG, MARÍA LAURA

ORGANIC & BIOMOLECULAR CHEMISTRY

ROYAL SOC CHEMISTRY

Año: 2021 vol. 19 p. 6455 - 6467

1477-0520

Herein we report the synthesis of an octavalent glycocluster exposing a thiodisaccharide mimetic of the repetitive unit of hyaluronic acid, βSGlcA(1→3)βSGlcNAc, constructed on a calix[4]resorcinarene scaffold by CuAAC reaction of suitable precursors. This glycocluster showed a strong tendency to self-aggregation. DOSY-NMR and DLS experiments demonstrated the formation of spherical micelles of d  6.2 nm in good agreement. TEM micrographs showed the presence of particles of different sizes, depending on the pH of the starting solution, thus, evidencing that the negative charge on the micelle surface due to ionization of the GlcA residues, plays an important role in the aggregation process. STD-NMR and DLS experiments provided evidence of the interaction between the synthetic glycocluster and Langerin, a relevant C-type lectin. This interaction was not observed in the STD-NMR experiments performed with the basic disaccharide, supporting evidence for multivalent effect