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 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Chemistry: A European Journal
Vol/bind	17
Udgave nummer	26
Sider (fra-til)	7198-7204
Antal sider	7
ISSN	0947-6539
DOI	https://doi.org/10.1002/chem.201100495
Status	Udgivet - 20 jun. 2011

Adgang til dokumentet

10.1002/chem.201100495

Citationsformater

@article{1e0a41574ce34d298359bc59fd5e317d,

title = "Controlled self-assembly of re-engineered insulin by FeII",

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.",

author = "Munch, {Henrik Kofoed} and Heide, {S{\o}ren Thiis} and Christensen, {Niels Johan} and Thomas H{\o}eg-Jensen and Thulstrup, {Peter Waaben} and Jensen, {Knud J{\o}rgen}",

year = "2011",

month = jun,

day = "20",

doi = "10.1002/chem.201100495",

language = "English",

volume = "17",

pages = "7198--7204",

journal = "Chemistry: A European Journal",

issn = "0947-6539",

publisher = "Wiley - V C H Verlag GmbH & Co. KGaA",

number = "26",

}

TY - JOUR

T1 - Controlled self-assembly of re-engineered insulin by FeII

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.

U2 - 10.1002/chem.201100495

DO - 10.1002/chem.201100495

M3 - Journal article

C2 - 21626587

SN - 0947-6539

VL - 17

SP - 7198

EP - 7204

JO - Chemistry: A European Journal

JF - Chemistry: A European Journal

IS - 26

ER -

Controlled self-assembly of re-engineered insulin by FeII

Abstract

Adgang til dokumentet

Fingeraftryk

Citationsformater

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