中国石油大学徐海团队报道了基于d/l氨基酸交替的特殊α-片构象的肽自组装。相关研究成果于2022年11月8日发表在《美国化学会杂志》。

肽自组装是一个层级结构过程，在初始阶段形成的二级结构在决定后续组装过程和最终结构排序中起着关键作用。不寻常的二级结构有望成为开发具有独特性质的新型超分子结构的来源。

该文中，研究人员报道了一种基于不寻常的α-片二级结构的新型肽自组装策略的设计。鉴于亮氨酸形成螺旋构象的强烈倾向及其高疏水性，设计了两种具有交替l型和d型氨基酸的短双亲肽Ac-LDLLDLK-NH2和Ac-DLLDLLDK-NH2。显微成像、中子散射和光谱测量表明，两种异手性肽形成高度有序的宽纳米管和单层厚度的螺旋带，与由同手性肽Ac-LLLLK-NH2形成的扭曲纳米纤维形成鲜明对比。从单体到三聚体的分子动力学模拟表明，这两种杂肽折叠成α-片而不是β-片，在低聚物模拟中，β-片很容易堆积成管状结构。基于α-片低聚物的模拟圆二色光谱验证了所提出的α-片二级结构。

研究结果为基于不寻常的α-片状二级结构的、具有新颖性质的高阶肽组件的合理设计提供了重要基础。

附：英文原文

Title: Peptide Self-Assemblies from Unusual α-Sheet Conformations Based on Alternation of d/l Amino Acids

Author: Peng Zhou, Xuzhi Hu, Jie Li, Yan Wang, Henghao Yu, Zhaoyu Chen, Dong Wang, Yurong Zhao, Stephen M. King, Sarah E. Rogers, Jiqian Wang, Jian Ren Lu, Hai Xu

Issue&Volume: November 8, 2022

Abstract: Peptide self-assembly is a hierarchical process during which secondary structures formed in the initial stages play a critical role in determining the subsequent assembling processes and final structural ordering. Unusual secondary structures hold promise as a source to develop novel supramolecular architectures with unique properties. In this work, we report the design of a new peptide self-assembly strategy based on unusual α-sheet secondary structures. In light of the strong propensity of leucine toward forming helical conformations and its high hydrophobicity, we design two short amphiphilic peptides Ac-LDLLDLK-NH2 and Ac-DLLDLLDK-NH2 with alternating l- and d-form amino acids. Microscopic imaging, neutron scattering, and spectroscopic measurements indicate that the two heterochiral peptides form highly ordered wide nanotubes and helical ribbons with monolayer thickness, in sharp contrast to twisted nanofibrils formed by the homochiral peptide Ac-LLLLK-NH2. Molecular dynamics simulations from monomers to trimers reveal that the two heteropeptides fold into α-sheets instead of β-sheets, which readily pack into tubular architectures in oligomer simulations. Simulated circular dichroism spectra based on α-sheet oligomers validate the proposed α-sheet secondary structures. These results form an important basis for the rational design of higher-order peptide assemblies with novel properties based on unusual α-sheet secondary structures.

DOI: 10.1021/jacs.2c08425

Source: https://pubs.acs.org/doi/10.1021/jacs.2c08425