TY - JOUR

T1 - Construction of insulin 18-mer nanoassemblies driven by coordination to Iron(II) and Zinc(II) ions at distinct sites

AU - Munch, Henrik Kofoed

AU - Nygård, Jesper

AU - Christensen, Niels Johan

AU - Engelbrekt, Christian

AU - Østergaard, Mads

AU - Porsgaard, Trine

AU - Hoeg-Jensen, Thomas

AU - Zhang, Jingdong

AU - Arleth, Lise

AU - Thulstrup, Peter Waaben

AU - Jensen, Knud Jørgen

N1 - [QDev]

PY - 2016

Y1 - 2016

N2 - 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 ZnII-binding hexamers to SA into trimers of hexamers, [[HI-bipy]6]3, driven by octahedral coordination to a FeII 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 FeII than ZnII ions, enabling control of the hexamer formation with ZnII and the formation of trimers of hexamers with FeII ions. This precise control of protein SA to give oligomers of oligomers provides nanoscale structures with potential applications in nanomedicine.

AB - 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 ZnII-binding hexamers to SA into trimers of hexamers, [[HI-bipy]6]3, driven by octahedral coordination to a FeII 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 FeII than ZnII ions, enabling control of the hexamer formation with ZnII and the formation of trimers of hexamers with FeII ions. This precise control of protein SA to give oligomers of oligomers provides nanoscale structures with potential applications in nanomedicine.

KW - Atomic force microscopy

KW - Insulin

KW - Nanostructures

KW - Self-assembly

KW - Small-angle X-ray scattering

U2 - 10.1002/anie.201509088

DO - 10.1002/anie.201509088

M3 - Letter

C2 - 26762534

AN - SCOPUS:84954341798

VL - 55

SP - 2378

EP - 2381

JO - Angewandte Chemie International Edition

JF - Angewandte Chemie International Edition

SN - 1433-7851

IS - 7

ER -