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The role of aromatic residues in controlling the supramolecular chirality of short amphiphilic peptides

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Abstract

Although the relationship between molecular and supramolecular chirality remains elusive, the existing results have demonstrated the vital role of hydrophilic motifs in controlling the supramolecular handedness of peptide nanofibrils compared with hydrophobic ones. However, unlike conventional hydrophobic residues, we speculate that aromatic hydrophobic residues are mostly likely to play a unique role in regulating the supramolecular handedness because the π−π stacking interactions of their side chains are directional like hydrogen bonding and can direct high levels of self-assembly due to the geometric confining of aromatic rings. To confirm this hypothesis, we here design a series of amphiphilic short peptides, with their hydrophobic motifs being composed of aromatic residues. Their short lengths not only favor their structural stability, synthesis, and sequence variation but also enable us to readily link their molecular and supramolecular structures. Through the combination of experiments and theoretical simulations, we demonstrate that the peptides containing L-form aromatic residues form left-handed nanofibrils while those containing D-form aromatic residues assemble into right-handed ones, irrespective of the chirality of their C-terminal hydrophilic residue. Theoretical calculations revealed that the stacking of aromatic side chains between β-strands directed the twisting direction of the β-sheets formed, with L- and D-form phenylalanine side chains stacking in a clockwise and anti-clockwise way, and more ordered and stronger aromatic stacking for homochiral peptides facilitated the formation of nanofibrils with a marked tubular feature. This study has bridged the knowledge gap in our understanding of how aromatic residues affect the supramolecular chirality of short peptides.

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Acknowledgements

This work was supported by the National Natural Science Foundation (Nos. 22172193, 22072181, and U1832108), a joint Innovate UK-Syngenta funded project under knowledge transfer partnership (No. KTP12697) and an EPSRC IAA 377 grant (No. R128362) with Arxada. We acknowledge the use of the resources of the China Spallation Neutron Source in Dongguan of Guangdong Province of China.

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Authors and Affiliations

  1. Department of Biological and Energy Chemical Engineering, China University of Petroleum (East China), Qingdao, 266580, China

    Hao Qi, Kai Qi, Yurong Zhao, Jiqian Wang & Hai Xu

  2. College of Life Science, Nankai University, Tianjin, 300071, China

    Jie Li & Chunqiu Zhang

  3. Spallation Neutron Source Science Center, Chinese Academy of Sciences (CAS), Dongguan, 523803, China

    Chunyong He & Yubin Ke

  4. Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, China

    Chunyong He & Yubin Ke

  5. Biological Physics Group, Department of Physics and Astronomy, The University of Manchester, Manchester, M13 9PL, UK

    Mingrui Liao, Xuzhi Hu & Jian R. Lu

  6. School of Material Science and Engineering, China University of Petroleum (East China), Qingdao, 266580, China

    Jun Zhang

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  1. Hao Qi
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  3. Jie Li
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Correspondence to Jiqian Wang or Hai Xu.

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Qi, H., Qi, K., Li, J. et al. The role of aromatic residues in controlling the supramolecular chirality of short amphiphilic peptides. Nano Res. 16, 12230–12237 (2023). https://doi.org/10.1007/s12274-023-5783-y

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