title: Construction of Insulin 18-mer Nanoassemblies Driven by Coordination to Iron(II) and Zinc(II) Ions at Distinct Sites.
abstract: 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.
authors.affiliation: Department of Chemistry, University of Copenhagen, Denmark.
authors.forename: Henrik K
authors.initials: HK
authors.lastname: Munch
authors.affiliation: MAX-lab, Lund University, Sweden.|Niels Bohr Institute, University of Copenhagen, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Nygaard
authors.affiliation: Department of Chemistry, University of Copenhagen, Denmark.
authors.forename: Niels Johan
authors.initials: NJ
authors.lastname: Christensen
authors.affiliation: Department of Chemistry, Technical University of Denmark, Kgs. Lyngby, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Engelbrekt
authors.affiliation: Department of Chemistry, University of Copenhagen, Denmark.
authors.forename: Mads
authors.initials: M
authors.lastname: Østergaard
authors.affiliation: Novo Nordisk A/S, 2760, Maaloev, Denmark.
authors.forename: Trine
authors.initials: T
authors.lastname: Porsgaard
authors.affiliation: Novo Nordisk A/S, 2760, Maaloev, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hoeg-Jensen
authors.affiliation: Department of Chemistry, Technical University of Denmark, Kgs. Lyngby, Denmark.
authors.forename: Jingdong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Niels Bohr Institute, University of Copenhagen, Denmark.
authors.forename: Lise
authors.initials: L
authors.lastname: Arleth
authors.affiliation: Department of Chemistry, University of Copenhagen, Denmark.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Thulstrup
authors.affiliation: Department of Chemistry, University of Copenhagen, Denmark. kjj@chem.ku.dk.
authors.forename: Knud J
authors.initials: KJ
authors.lastname: Jensen
mesh_terms: D000595:Amino Acid Sequence; D005296:Ferrous Compounds / Q000737:chemistry*; D007328:Insulin / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D008969:Molecular Sequence Data; D049329:Nanostructures; D015032:Zinc / Q000737:chemistry*
chemical_list: D005296:Ferrous Compounds; D007328:Insulin; D015032:Zinc
keywords: atomic force microscopy; insulin; nanostructures; self-assembly; small-angle X-ray scattering