| Perfluoroalkyl Chains Direct Novel Self-Assembly of Insulin. | |
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MedLine Citation:
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PMID: 22129241 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The self-assembly of biopharmaceutical peptides into multimeric, nano-scale 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 inter-molecular 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 ZnII 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 perfluroalkyl 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 ZnII mediated hexamer formation with fluorous interactions, is a promising tool to control the formation of high molecular weight complexes of insulin andd potentially other proteins. |
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Authors:
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Knud J Jensen; Leila Malik; Jesper Nygaard; Rasmus Høiberg-Nielsen; Lise Arleth; Thomas Hoeg-Jensen |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-30 |
Journal Detail:
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Title: Langmuir : the ACS journal of surfaces and colloids Volume: - ISSN: 1520-5827 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-12-1 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9882736 Medline TA: Langmuir Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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