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 - 2016/2/12
Y1 - 2016/2/12
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
SN - 1433-7851
VL - 55
SP - 2378
EP - 2381
JO - Angewandte Chemie International Edition
JF - Angewandte Chemie International Edition
IS - 7
ER -