Construction of Insulin 18-mer Nanoassemblies Driven by Coordination to Iron(II) and Zinc(II) Ions at Distinct Sites

Controlled self-assembly (SA) of proteins offers the possibility to tune their properties or to create new materials. Herein, we present the synthesis of a modified human insulin (HI) with two distinct metal-ion binding sites, one native, the other abiotic, enabling hierarchical SA through coordination with two different metal ions. Selective attachment of an abiotic 2,2'-bipyridine (bipy) ligand to HI, yielding HI-bipy, enabled Zn(II) -binding hexamers to SA into trimers of hexamers, [[HI-bipy]6 ]3 , driven by octahedral coordination to a Fe(II) ion. The structures were studied in solution by small-angle X-ray scattering and on surfaces with AFM. The abiotic metal ligand had a higher affinity for Fe(II) than Zn(II) ions, enabling control of the hexamer formation with Zn(II) and the formation of trimers of hexamers with Fe(II) ions. This precise control of protein SA to give oligomers of oligomers provides nanoscale structures with potential applications in nanomedicine. (Less)