State Key Laboratory of Heavy Oil Processing and Department of Biological and Energy Chemical Engineering, China University of Petroleum (East China), 66 Changjiang West Road, Qingdao, 266580, China.
Department of Civil Engineering, Qingdao University of Technology, Qingdao, 266033, China.
Nat Commun. 2024 Jul 23;15(1):6186. doi: 10.1038/s41467-024-50448-0.
Although hydrophobic interactions provide the main driving force for initial peptide aggregation, their role in regulating suprastructure handedness of higher-order architectures remains largely unknown. We here interrogate the effects of hydrophobic amino acids on handedness at various assembly stages of peptide amphiphiles. Our studies reveal that relative to aliphatic side chains, aromatic side chains set the twisting directions of single β-strands due to their strong steric repulsion to the backbone, and upon packing into multi-stranded β-sheets, the side-chain aromatic interactions between strands form the aromatic ladders with a directional preference. This ordering not only leads to parallel β-sheet arrangements but also induces the chiral flipping over of single β-strands within a β-sheet. In contrast, the lack of orientational hydrophobic interactions in the assembly of aliphatic peptides implies no chiral inversion upon packing into β-sheets. This study opens an avenue to harness peptide aggregates with targeted handedness via aromatic side-chain interactions.
虽然疏水相互作用提供了初始肽聚集的主要驱动力，但它们在调节高级结构超结构手性方面的作用在很大程度上仍然未知。在这里，我们研究了疏水性氨基酸对肽两亲物各个组装阶段手性的影响。我们的研究表明，与脂肪族侧链相比，芳香族侧链由于与骨架的强烈空间排斥作用而设定了单 β-链的扭曲方向，并且在包装成多股 β-折叠时，链之间的侧链芳香族相互作用形成具有方向性偏好的芳香族梯级。这种有序不仅导致平行的β-片层排列，而且诱导β-片层内单个β-链的手性翻转。相比之下，脂肪族肽组装中缺乏定向疏水相互作用意味着在包装成β-片层时不会发生手性反转。这项研究为通过芳香族侧链相互作用利用具有靶向手性的肽聚集物开辟了一条途径。
