A modular synthetic platform for the construction of protein-based supramolecular polymers via coiled-coil self-assembly

Abstract

Programmed biomolecular self-assembly is a powerful method for the construction of designed supramolecular materials. Here, we show that branched ∼8 kDa subunits composed of α-helical coiled-coil protein domains cross-linked at their midpoints by an organic bridging group can form defined supramolecular polymer assemblies in aqueous solution. The subunits are accessible by a modular and convergent synthetic route based on the chemoselective ligation of unprotected peptide building blocks. Systematic characterization of solution folding and self-assembly demonstrate that the properties of the assemblies (e.g., chain length, hydrodynamic radius) are sensitive to both the structure of the organic bridge and the sequence of the protein domain. These findings raise the possibility of the rational design of a family of supramolecular materials with tunable properties based on well-established sequence–folding relationships in coiled-coil proteins.