3D ² Self-Assembling Janus Peptide Dendrimers with Tailorable Supermultivalency

The self-assembly of peptides enables the construction of self-assembled peptide nanostructures (SPNs) with chemical composition similar to those of natural proteins; however, the structural complexity and functional properties of SPNs are far beneath those of natural proteins. One of the most fundamental challenges in fabricating more elaborate SPNs lies in developing building blocks that are simultaneously more complex and relatively easy to synthesize. Here, the development of self-assembling Janus peptide dendrimers (JPDs) is reported, which have fully 3D structures similar to those of globular proteins. For the reliable and convenient synthesis of JPDs, a solid-phase bifurcation synthesis method is devised. The self-assembly behavior of JPDs is unique because only the dendrimer generation and not the weight fraction dictates the morphology of SPNs. The coassembly of two JPD building blocks provides an opportunity not only to enlarge the morphological repertoire in a predictable manner but also to discover SPNs with unusual and interesting morphologies. Because JPD assemblies have dual multivalency, i.e., supramolecular and unimolecular multivalency, the JPD system enables the statistical selection of materials with high avidity for the desired cell types and possibly any target receptors.