Enantiomeric β-sheet peptides from Aβ form homochiral pleated β-sheets rather than heterochiral rippled β-sheets.
Enantiomeric β-sheet peptides from Aβ form homochiral pleated β-sheets rather than heterochiral rippled β-sheets.
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DOI：
10.1039/d2sc02080g
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发表时间：
2022-07-06
期刊：
影响因子：
8.4
通讯作者：
中科院分区：
文献类型：
--
作者：
1953年，鲍林和科里假设了由d-和l-肽链混合而成的“波纹状”β-折叠，作为对现在已经确立的“褶皱状”β-折叠结构的一种假设替代，他们提出将其作为全l-蛋白质的组成部分。在过去的十年中，对波纹β-折叠的兴趣日益增长，导致了用于生物医学应用的d-和l-肽的混合物的开发，并且已经出现了一种理论，即对映体β-折叠肽的混合物优选以异手性方式共组装以形成波纹β-折叠。对映体β折叠肽更喜欢以同手性方式自组装形成折叠β折叠的相互矛盾的报道很感兴趣，我们开始使用来自Aβ17-23和Aβ30-36的两种β折叠肽（肽1a和1b）来解决这一争议。这些肽中的每一种自组装以形成四聚体，所述四聚体包括在水溶液中的β-折叠二聚体的夹层。通过溶液相NMR光谱，我们表征了肽1a和1b与其各自的d-对映异构体，肽ent-1a和ent-1b混合时形成的不同物种。1H NMR、DOSY和1H，15 N-HSQC实验表明，混合肽1a和ent-1a导致主要形成纯手性四聚体，具有较小部分的新的异手性四聚体，并且混合肽1b和ent-1b不会导致任何可检测的异手性组装。15 N-编辑的NOESY揭示了由肽1a和ent-1a形成的异手性四聚体由两个同手性二聚体组成。总的来说，Aβ衍生肽的这些NMR研究提供了令人信服的证据，即对映体β折叠肽更喜欢在水溶液中以同手性方式自组装。在水溶液中，衍生自Aβ的l-和d-大环β-折叠肽的混合物自组装以形成纯手性折叠β-折叠，但不共组装以形成异手性波纹β-折叠。
In 1953, Pauling and Corey postulated “rippled” β-sheets, composed of a mixture of d- and l-peptide strands, as a hypothetical alternative to the now well-established structures of “pleated” β-sheets, which they proposed as a component of all-l-proteins. Growing interest in rippled β-sheets over the past decade has led to the development of mixtures of d- and l-peptides for biomedical applications, and a theory has emerged that mixtures of enantiomeric β-sheet peptides prefer to co-assemble in a heterochiral fashion to form rippled β-sheets. Intrigued by conflicting reports that enantiomeric β-sheet peptides prefer to self-assemble in a homochiral fashion to form pleated β-sheets, we set out address this controversy using two β-sheet peptides derived from Aβ17–23 and Aβ30–36, peptides 1a and 1b. Each of these peptides self-assembles to form tetramers comprising sandwiches of β-sheet dimers in aqueous solution. Through solution-phase NMR spectroscopy, we characterize the different species formed when peptides 1a and 1b are mixed with their respective d-enantiomers, peptides ent-1a and ent-1b. 1H NMR, DOSY, and 1H,15N-HSQC experiments reveal that mixing peptides 1a and ent-1a results in the predominant formation of homochiral tetramers, with a smaller fraction of a new heterochiral tetramer, and mixing peptides 1b and ent-1b does not result in any detectable heterochiral assembly. 15N-edited NOESY reveals that the heterochiral tetramer formed by peptides 1a and ent-1a is composed of two homochiral dimers. Collectively, these NMR studies of Aβ-derived peptides provide compelling evidence that enantiomeric β-sheet peptides prefer to self-assemble in a homochiral fashion in aqueous solution. In aqueous solution, mixtures of l- and d- macrocyclic β-sheet peptides derived from Aβ self-assemble to form homochiral pleated β-sheets but do not co-assemble to form heterochiral rippled β-sheets.
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8.4
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