来自 Aβ 的对映体 β-折叠肽形成同手性折叠 β-折叠而不是异手性波纹 β-折叠,Chemical Science

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来自 Aβ 的对映体 β-折叠肽形成同手性折叠 β-折叠而不是异手性波纹 β-折叠
Chemical Science ( IF 7.6 ) Pub Date : 2022-05-31 , DOI: 10.1039/d2sc02080g
Xingyue Li ₁ , Stephanie E Rios ₁ , James S Nowick _{1,

2}

Affiliation

1953 年，Pauling 和 Corey 假设“波纹状”β-折叠由D和L-肽链的混合物组成，作为现在公认的“折叠”β-折叠结构的假设替代方案，他们提出所有L蛋白的组成部分。在过去十年中，人们对波纹状 β-折叠的兴趣日益浓厚，导致了D - 和L混合物的发展- 用于生物医学应用的肽，并且出现了一种理论，即对映体 β-折叠肽的混合物更喜欢以异手性方式共同组装以形成波纹状 β-折叠。对映体 β 折叠肽更喜欢以纯手性方式自组装形成褶皱 β 折叠的相互矛盾的报道引起了我们的兴趣，我们开始使用源自 Aβ 17–23 和 Aβ 30–36 的两种 β 折叠肽来_解决这一_争议，肽1a和1b。这些肽中的每一种都在水溶液中自组装形成四聚体，该四聚体包含 β-折叠二聚体的三明治。通过溶液相 NMR 光谱，我们表征了肽1a和1b形成的不同物种与它们各自的D对映异构体、肽ent - 1a和ent - 1b混合。¹ H NMR、DOSY 和¹ H, ¹⁵ N-HSQC 实验表明，混合肽1a和ent - 1a会导致主要形成纯手性四聚体，以及一小部分新的异手性四聚体，以及混合肽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 揭示了肽形成的异手性四聚体1a和ent - 1a由两个同手性二聚体组成。总的来说，这些 Aβ 衍生肽的 NMR 研究提供了令人信服的证据，证明对映体 β-折叠肽更喜欢在水溶液中以纯手性方式自组装。

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Enantiomeric β-sheet peptides from Aβ form homochiral pleated β-sheets rather than heterochiral rippled β-sheets

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 Aβ_17–23 and Aβ_30–36, 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.

更新日期：2022-05-31

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