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231224s2012 xx |||||o 00| ||eng c |
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|a 10.1021/la203042c
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|a eng
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|a Malik, Leila
|e verfasserin
|4 aut
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|a Perfluoroalkyl chains direct novel self-assembly of insulin
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|c 2012
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|a Text
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|a ƒaComputermedien
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|a Date Completed 25.04.2012
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|a Date Revised 10.01.2012
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|a published: Print-Electronic
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|a Citation Status MEDLINE
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|a The self-assembly of biopharmaceutical peptides into multimeric, nanoscale objects, as well as their disassembly to monomers, is central for their mode of action. Here, we describe a bioorthogonal strategy, using a non-native recognition principle, for control of protein self-assembly based on intermolecular fluorous interactions and demonstrate it for the small protein insulin. Perfluorinated alkyl chains of varying length were attached to desB30 human insulin by acylation of the ε-amine of the side-chain of LysB29. The insulin analogues were formulated with Zn(II) and phenol to form hexamers. The self-segregation of fluorous groups directed the insulin hexamers to self-assemble. The structures of the systems were investigated by circular dichroism (CD) spectroscopy and synchrotron small-angle X-ray scattering. Also, the binding affinity to the insulin receptor was measured. Interestingly, varying the length of the perfluoroalkyl chain provided three different scenarios for self-assembly; the short chains hardly affected the native hexameric structure, the medium-length chains induced fractal-like structures with the insulin hexamer as the fundamental building block, while the longest chains lead to the formation of structures with local cylindrical geometry. This hierarchical self-assembly system, which combines Zn(II) mediated hexamer formation with fluorous interactions, is a promising tool to control the formation of high molecular weight complexes of insulin and potentially other proteins
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|a Journal Article
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|a Insulin
|2 NLM
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|a Nygaard, Jesper
|e verfasserin
|4 aut
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|a Hoiberg-Nielsen, Rasmus
|e verfasserin
|4 aut
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|a Arleth, Lise
|e verfasserin
|4 aut
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|a Hoeg-Jensen, Thomas
|e verfasserin
|4 aut
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|a Jensen, Knud J
|e verfasserin
|4 aut
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|i Enthalten in
|t Langmuir : the ACS journal of surfaces and colloids
|d 1985
|g 28(2012), 1 vom: 10. Jan., Seite 593-603
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|x 1520-5827
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|g volume:28
|g year:2012
|g number:1
|g day:10
|g month:01
|g pages:593-603
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|u http://dx.doi.org/10.1021/la203042c
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