Here we described C-type lectin-oriented surfaces for SPR analysis. They allow the preservation of receptor topology, accessibility of binding sites, better evaluation of high avidity compounds and assessment of multivalent effect at cell surface.

Glycan-protein interactions control numerous biological events from cell-cell recognition and signaling to pathogen host cell attachment for infections. To infect cells, some viruses bind to immune cells thanks to DC-SIGN (dendritic cell [DC]-specific ICAM3-grabbing non-integrin) C-type lectin expressed on dendritic and macrophage cell membrane, via their envelope protein. Prevention of this infectious interaction is a serious therapeutic option. Here, we describe the synthesis of first water-soluble tetravalent fucocluster pseudopeptide-based thiacalixarene 1,3-alternate as viral antigen mimics designed for the inhibition of DC-SIGN, to prevent viral particle uptake. Their preparation exploits straightforward convergent strategies involving one pot Ugi four-component (Ugi-4CR) and azido-alkyne click chemistry reactions as key steps. Surface plasmon resonance showed strong inhibition of DC-SIGN interaction properties by tetravalent ligands designed with high relative potencies and β avidity factors. All ligands block DC-SIGN active sites at nanomolar IC 50 preventing cis-cell infection by Ebola viral particles pseudotyped with EBOV glycoprotein (Zaïre species of Ebola virus) on Jurkat cells that express DC-SIGN. In addition, we observed strong inhibition of DC-SIGN/human cytomegalovirus (HCMV)-gB recombinant glycoprotein interaction. This finding opens the way to the simple development of new models of water-soluble glycocluster-based thia-calixarene with wide-range antimicrobial activities.