Multivalent Cluster Nanomolecules for Inhibiting Protein–Protein Interactions

Multivalent
protein–protein interactions serve
central roles in many essential biological processes, ranging from
cell signaling and adhesion to pathogen recognition. Uncovering the
rules that govern these intricate interactions is important not only
to basic biology and chemistry but also to the applied sciences where
researchers are interested in developing molecules to promote or inhibit
these interactions. Here we report the synthesis and application of
atomically precise inorganic cluster nanomolecules consisting of an
inorganic core and a covalently linked densely packed layer of saccharides.
These hybrid agents are stable under biologically relevant conditions
and exhibit multivalent binding capabilities, which enable us to study
the complex interactions between glycosylated structures and a dendritic
cell lectin receptor. Importantly, we find that subtle changes in
the molecular structure lead to significant differences in the nanomolecule’s
protein-binding properties. Furthermore, we demonstrate an example
of using these hybrid nanomolecules to effectively inhibit protein–protein
interactions in a human cell line. Ultimately, this work reveals an
intricate interplay between the structural design of multivalent agents
and their biological activities toward protein surfaces.