近日，中国石油大学徐海团队研究了立体互补驱动短肽立体异构体的强共组装。2025年4月21日，《美国化学会杂志》发表了这一成果。

立体互补性在维持蛋白质结构和识别中起着至关重要的作用。然而，在超分子化学和材料科学中，精确控制不同长度尺度上的空间互补性和相关相互作用，以构建高阶肽和蛋白质纳米结构和纳米材料，仍然是一个重大挑战。通过设计的芳香短肽立体异构体的共组装，研究组以可控的方式将特定的π-π堆叠相互作用整合到β-折叠内肽链之间的面部互补性中。

芳香侧链之间的高度立体互补性导致这些肽立体异构体具有很强的共组装能力，超分子形态和大小发生了巨大变化。研究组还揭示了它们的联合体的超结构手性代码，并将其与β-片两面上的侧链几何互补性和分布联系起来。这项工作不仅强调了空间互补性在肽折叠中的重要性，而且为通过子片水平的空间互补性制造复杂的肽β-片组装体提供了一个范例。

附：英文原文

Title: Steric Complementarity Drives Strong Co-Assembly of Short Peptide Stereoisomers

Author: Hao Qi, Kai Qi, Yan Wang, Xinfeng Ju, Yuchun Han, Stephen M. King, Sarah E. Rogers, Yilin Wang, Feng Zhou, Jian R. Lu, Hai Xu, Xuzhi Hu

Issue&Volume: April 21, 2025

Abstract: Steric complementarity plays an essential role in maintaining protein architecture and recognition. In supramolecular chemistry and material science, however, it remains a major challenge to precisely control steric complementarity and associated interactions across different length scales for the construction of higher-order peptide and protein nanostructures and nanomaterials. Through coassembly of designed aromatic short peptide stereoisomers, we here incorporate specific π–π stacking interactions into facial complementarity between peptide strands within a β-sheet in a controllable manner. The high steric complementarity between aromatic side chains leads to strong coassembly capabilities of these peptide stereoisomers and dramatic changes in supramolecular morphology and size. We also unravel suprastructural handedness codes for their coassemblies and relate them to the side chain geometric complementarity and distribution on the two faces of the β-sheet. This work not only highlights the importance of steric complementarity in peptide folding but also provides a paradigm for the fabrication of intricate peptide β-sheet assemblies via steric complementarity at the subsheet level.

DOI: 10.1021/jacs.4c17497

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.4c17497