Journal article
Controlled self-assembly of re-engineered insulin by Fe(II)
IGM, Faculty of Life Sciences, University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg, Denmark.1
Self-assembly of proteins mediated by metal ions is crucial in biological systems and a better understanding and novel strategies for its control are important. An abiotic metal ion ligand in a protein offers the prospect of control of the oligomeric state, if a selectivity over binding to the native side chains can be achieved.
Insulin binds Zn(II) to form a hexamer, which is important for its storage in vivo and in drug formulations. We have re-engineered an insulin variant to control its self-assembly by covalent attachment of 2,2'-bipyridine. The use of Fe(II) provided chemoselective binding over the native site, forming a homotrimer in a reversible manner, which was easily followed by the characteristic color of the Fe(II) complex.
This provided the first well-defined insulin trimer and the first insulin variant for which self-assembly can be followed visually.
Language: | English |
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Publisher: | WILEY‐VCH Verlag |
Year: | 2011 |
Pages: | 7198-204 |
ISSN: | 15213757 , 00448249 , 09476539 and 15213765 |
Types: | Journal article |
DOI: | 10.1002/chem.201100495 |
ORCIDs: | Christensen, Niels Johan , Thulstrup, Peter W and Jensen, Knud J |