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Membrane active Janus-oligomers of β3-peptides
Chemical Science ( IF 7.6 ) Pub Date : 2020-06-15 , DOI: 10.1039/d0sc01344g Imola Cs Szigyártó 1 , Judith Mihály 1 , András Wacha 1 , Dóra Bogdán 1, 2 , Tünde Juhász 1 , Gergely Kohut 1, 3 , Gitta Schlosser 3 , Ferenc Zsila 1 , Vlada Urlacher 4 , Zoltán Varga 1 , Ferenc Fülöp 5 , Attila Bóta 1 , István Mándity 1, 2 , Tamás Beke-Somfai 1, 6
Chemical Science ( IF 7.6 ) Pub Date : 2020-06-15 , DOI: 10.1039/d0sc01344g Imola Cs Szigyártó 1 , Judith Mihály 1 , András Wacha 1 , Dóra Bogdán 1, 2 , Tünde Juhász 1 , Gergely Kohut 1, 3 , Gitta Schlosser 3 , Ferenc Zsila 1 , Vlada Urlacher 4 , Zoltán Varga 1 , Ferenc Fülöp 5 , Attila Bóta 1 , István Mándity 1, 2 , Tamás Beke-Somfai 1, 6
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Self-assembling peptides offer a versatile set of tools for bottom-up construction of supramolecular biomaterials. Among these compounds, non-natural peptidic foldamers experience increased focus due to their structural variability and lower sensitivity to enzymatic degradation. However, very little is known about their membrane properties and complex oligomeric assemblies – key areas for biomedical and technological applications. Here we designed short, acyclic β3-peptide sequences with alternating amino acid stereoisomers to obtain non-helical molecules having hydrophilic charged residues on one side, and hydrophobic residues on the other side, with the N-terminus preventing formation of infinite fibrils. Our results indicate that these β-peptides form small oligomers both in water and in lipid bilayers and are stabilized by intermolecular hydrogen bonds. In the presence of model membranes, they either prefer the headgroup regions or they insert between the lipid chains. Molecular dynamics (MD) simulations suggest the formation of two-layered bundles with their side chains facing opposite directions when compared in water and in model membranes. Analysis of the MD calculations showed hydrogen bonds inside each layer, however, not between the layers, indicating a dynamic assembly. Moreover, the aqueous form of these oligomers can host fluorescent probes as well as a hydrophobic molecule similarly to e.g. lipid transfer proteins. For the tested, peptides the mixed chirality pattern resulted in similar assemblies despite sequential differences. Based on this, it is hoped that the presented molecular framework will inspire similar oligomers with diverse functionality.
中文翻译：
β3-肽的膜活性 Janus-寡聚体
自组装肽为自下而上构建超分子生物材料提供了一套多功能工具。在这些化合物中，非天然肽折叠体由于其结构可变性和对酶降解的敏感性较低而受到更多关注。然而，对于它们的膜特性和复杂的低聚组装体——生物医学和技术应用的关键领域——知之甚少。在这里，我们设计了短的无环 β 3-具有交替氨基酸立体异构体的肽序列以获得一侧具有亲水性带电残基和另一侧具有疏水性残基的非螺旋分子，其中N-末端防止形成无限原纤维。我们的结果表明，这些 β-肽在水和脂质双层中均形成小的低聚物，并通过分子间氢键稳定。在模型膜存在的情况下，它们要么更喜欢头部区域，要么插入脂质链之间。分子动力学 (MD) 模拟表明，在水和模型膜中进行比较时，形成了两层束，其侧链朝向相反方向。对 MD 计算的分析显示，每一层内部都有氢键，但层间没有氢键，表明存在动态组装。而且，例如脂质转移蛋白。对于测试的肽，混合手性模式导致相似的组装，尽管顺序不同。基于此，希望所提出的分子框架能够激发具有不同功能的类似低聚物。
更新日期：2020-07-08
中文翻译：
β3-肽的膜活性 Janus-寡聚体
自组装肽为自下而上构建超分子生物材料提供了一套多功能工具。在这些化合物中，非天然肽折叠体由于其结构可变性和对酶降解的敏感性较低而受到更多关注。然而，对于它们的膜特性和复杂的低聚组装体——生物医学和技术应用的关键领域——知之甚少。在这里，我们设计了短的无环 β 3-具有交替氨基酸立体异构体的肽序列以获得一侧具有亲水性带电残基和另一侧具有疏水性残基的非螺旋分子，其中N-末端防止形成无限原纤维。我们的结果表明，这些 β-肽在水和脂质双层中均形成小的低聚物，并通过分子间氢键稳定。在模型膜存在的情况下，它们要么更喜欢头部区域，要么插入脂质链之间。分子动力学 (MD) 模拟表明，在水和模型膜中进行比较时，形成了两层束，其侧链朝向相反方向。对 MD 计算的分析显示，每一层内部都有氢键，但层间没有氢键，表明存在动态组装。而且，例如脂质转移蛋白。对于测试的肽，混合手性模式导致相似的组装，尽管顺序不同。基于此，希望所提出的分子框架能够激发具有不同功能的类似低聚物。
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