Department of Pharmacy, Research Centre on Bioactive Peptides (CIRPeB), University of Naples "Federico II", Via Mezzocannone 16, 80134, Naples, Italy.
Institute of Biostructures and Bioimaging (IBB), CNR, Via Mezzocannone 16, 80134, Naples, Italy.
Soft Matter. 2018 Oct 17;14(40):8219-8230. doi: 10.1039/c8sm01441h.
The ability of peptides to self-assemble represents a valuable tool for the development of biomaterials of biotechnological and/or biomedical interest. Diphenylalanine homodimer (FF) and its analogues are among the most promising systems in this field. The longest Phe-based building block hitherto characterized is pentaphenylalanine (F5). We studied the aggregation propensity and the structural/morphological features of assemblies of zwitterionic hexaphenylalanine H+-F6-O- and of three variants characterized by different charged states of the terminal ends (Ac-F6-Amide, H+-F6-Amide and Ac-F6-O-). As previously observed for PEGylated hexaphenylalanine (PEG8-F6), all F6 variants show a strong tendency to form β-rich assemblies in which the structural motif is constituted by antiparallel β-strands in the cross-β framework. Extensive replica exchange molecular dynamics simulations carried out on a pairs of F6 peptides indicate that the antiparallel β-structure of the final assemblies is likely dictated by the preferred association modes of the individual chains in the very early stages of the aggregation process. Our data suggest that even very small F6 peptides are properly pre-organized and prone to the build-up of the final assembly.
肽的自组装能力为生物技术和/或生物医学领域的生物材料的发展提供了一种有价值的工具。二苯丙氨酸同型二聚体（FF）及其类似物是该领域最有前途的体系之一。迄今为止，所描述的最长的基于苯丙氨酸的构建块是五苯丙氨酸（F5）。我们研究了两性离子六苯丙氨酸 H+-F6-O-和三个具有不同末端电荷状态的变体（Ac-F6-Amide、H+-F6-Amide 和 Ac-F6-O-）组装体的聚集倾向和结构/形态特征。正如先前观察到的 PEG 化六苯丙氨酸（PEG8-F6）一样，所有 F6 变体都表现出强烈的形成富含β的组装体的趋势，其中结构基元由交叉-β 结构中的反平行β-链组成。在 F6 肽的一对肽上进行的广泛复制交换分子动力学模拟表明，最终组装体的反平行 β 结构可能由聚合过程的早期阶段中各个链的优选缔合模式决定。我们的数据表明，即使是非常小的 F6 肽也被适当预组织，并易于构建最终组装体。
