Perfluoroalkyl chains direct novel self-assembly of insulin.
Perfluoroalkyl chains direct novel self-assembly of insulin.
复制标题
全氟烷基链指导胰岛素的新型自组装。
DOI：
10.1021/la203042c
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
K. Jensen
中科院分区：
文献类型：
--
作者：
Leila Malik;J. Nygaard;Rasmus Høiberg;L. Arleth;T. Hoeg;K. Jensen
生物制药肽自组装成多聚体、纳米级物体，以及分解成单体，是其作用模式的核心。在这里，我们描述了一种生物正交策略，使用非天然识别原理，基于分子间氟相互作用控制蛋白质自组装，并在小蛋白胰岛素中进行了演示。通过 LysB29 侧链 ε-胺的酰化，将不同长度的全氟烷基链连接到 desB30 人胰岛素上。胰岛素类似物与 Zn(II) 和苯酚配制形成六聚体。氟基团的自分离引导胰岛素六聚体进行自组装。通过圆二色性（CD）光谱和同步加速器小角X射线散射研究了系统的结构。另外，还测量了与胰岛素受体的结合亲和力。有趣的是，改变全氟烷基链的长度为自组装提供了三种不同的情况；短链几乎不影响天然六聚体结构，中等长度的链诱导以胰岛素六聚体作为基本构建单元的分形结构，而最长的链导致形成具有局部圆柱形几何形状的结构。这种分层自组装系统将 Zn(II) 介导的六聚体形成与氟相互作用相结合，是控制胰岛素和潜在其他蛋白质的高分子量复合物形成的有前途的工具。
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.
影响因子：
2.9
作者：
Gottler, Lindsey M.;Bea, Roberto de la Salud;Marsh, E. Neil G.
通讯作者：
Marsh, E. Neil G.