A protein–foldamer supramolecular synthon for self-assembled hybrid architectures

Abstract

Constructing artificial assemblies that combine proteins and synthetic ligands has been hampered by the lack of protein–ligand interfaces that are sufficiently large and organized to enable precise structural control. Here ribosome display selection is used to identify a protein that binds a helical aromatic foldamer both tightly and selectively through a sizeable surface area. We used this complex as a supramolecular synthon to create well-defined hybrid foldamer–protein architectures. Examples include foldamers that bind two proteins and hold them at a precise distance, proteins that bind two foldamers and crystals in which proteins and foldamers are connected in cyclic or infinite arrays. The modularity of aromatic foldamers brings a further dimension to protein-based assemblies. A stable and modular artificial protein–foldamer helical supramolecular synthon enables the assembly of ordered architectures, in which the foldamer dictates protein orientation and spacing on the nanoscale.