Precision dendritic-supramolecular glycan assemblies for probing multivalent lectin interactions.

Multivalent glycan-protein binding events participate in various physiological functions including cell signaling, immune response, and pathogen-host recognition, among others. The complexity of these processes has driven sustained interest in developing densely functionalized glycan nanoassemblies to probe and modulate these important interactions. While synthetic glyconanomaterials have demonstrated significant promise in nanomedicine and biotechnology applications, achieving precise control over their architecture remains challenging. To address this limitation, we present a new method of synthesizing molecular glycan nanoassemblies by integrating the dense functionalization of dendritic architectures with the preorganized scaffolding of metallosupramolecular frameworks. A family of Fe(ii)-anchored superassemblies featuring 24, 36, and 72 peripheral mannosides was prepared and characterized by spectroscopic, microscopic, and light scattering techniques. These assemblies demonstrate strong binding with the lectins Concanavalin A (Con A) and Griffithsin (GRFT), as evaluated by isothermal titration calorimetry (ITC), with the 72-mannose derivative exhibiting low nanomolar binding affinity ( = 28 ± 4 nM for Con A; 12 ± 1 nM for GRFT). The high binding strength of these assemblies highlights the potential of integrating dendritic architectures with rigid metallosupramolecular cores to enhance lectin recognition. Our findings present a new framework for probing glycan protein interactions and offer insights into the design of hybrid glycoassemblies as biomedically-relevant tools.