Controlled self-assembly of re-engineered insulin by FeII

Henrik Kofoed Munch; Søren Thiis Heide; Niels Johan Christensen; Thomas Høeg-Jensen; Peter Waaben Thulstrup; Knud Jørgen Jensen

doi:10.1002/chem.201100495

Controlled self-assembly of re-engineered insulin by Fe^II

Henrik Kofoed Munch, Søren Thiis Heide, Niels Johan Christensen, Thomas Høeg-Jensen, Peter Waaben Thulstrup, Knud Jørgen Jensen

21 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Chemistry: A European Journal
Volume	17
Issue number	26
Pages (from-to)	7198-7204
Number of pages	7
ISSN	0947-6539
DOIs	https://doi.org/10.1002/chem.201100495
Publication status	Published - 20 Jun 2011

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abstract = "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 ZnII 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 FeII provided chemoselective binding over the native site, forming a homotrimer in a reversible manner, which was easily followed by the characteristic color of the FeII complex. This provided the first well-defined insulin trimer and the first insulin variant for which self-assembly can be followed visually.",

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AU - Munch, Henrik Kofoed

AU - Heide, Søren Thiis

AU - Christensen, Niels Johan

AU - Høeg-Jensen, Thomas

AU - Thulstrup, Peter Waaben

AU - Jensen, Knud Jørgen

PY - 2011/6/20

Y1 - 2011/6/20

N2 - 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 ZnII 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 FeII provided chemoselective binding over the native site, forming a homotrimer in a reversible manner, which was easily followed by the characteristic color of the FeII complex. This provided the first well-defined insulin trimer and the first insulin variant for which self-assembly can be followed visually.

AB - 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 ZnII 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 FeII provided chemoselective binding over the native site, forming a homotrimer in a reversible manner, which was easily followed by the characteristic color of the FeII complex. This provided the first well-defined insulin trimer and the first insulin variant for which self-assembly can be followed visually.

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DO - 10.1002/chem.201100495

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Controlled self-assembly of re-engineered insulin by FeII

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Controlled self-assembly of re-engineered insulin by Fe^II