Metal-peptidic cages—Helical oligoprolines generate highly anisotropic nanospaces with emergent isomer control

The self-assembly of metal-organic cages enables the rapid creation of atomically defined, three-dimensional, nanoscale architectures reminiscent of proteins. However, existing metal-organic cages are almost exclusively built from rigid and flat aromatic panels, limiting binding selectivity and, often, water solubility. Herein, we disclose a new class of cages—metal-peptidic cages—which utilize water-soluble, chiral, and helical oligoproline strands of varying lengths to generate highly anisotropic nanospaces. Further, we find that the formation of the cis isomer of the cage is strongly favored and is an emergent property of using complex and chiral building blocks in the formation of defined nanospaces. We demonstrate that the use of peptidic building blocks allows us to rapidly tune the size of the nanospace formed, from c. 1 to 4 nm, and that the use of biologically relevant components enables targeted binding of therapeutic molecules, highlighting the potential of these systems for selective drug delivery.</p