ジャーナル: Nano Lett / 年: 2026 タイトル: Conformational Adaptability and Thermostability in α/β-Peptide Fibrils Induced by β-Amino Acid Substitution. 著者: Yingshan Li / Danni Li / Yuxuan Yao / Kaien Liu / Qinyue Zhao / Yiling Zhang / Yongyi Xu / Dan Li / Bo Sun / Cong Liu / Bin Dai / 要旨: The self-assembly of peptides into amyloid fibrils enables the design of functional biomaterials, yet the conformational constraints of α-peptides limit the attainable supramolecular diversity. ...The self-assembly of peptides into amyloid fibrils enables the design of functional biomaterials, yet the conformational constraints of α-peptides limit the attainable supramolecular diversity. Here, we introduce β-amino acids, β-phenylalanine (β-Phe), and β-homophenylalanine (β-hPhe) into the reversible fibril-forming core sequence hnRAC1 to generate α/β-peptide variants with distinct architectures and enhanced thermal stability. Cryo-EM reveals that β-modified peptides assemble into polymorphic fibrils with cross-β structures that differ markedly from each other and from native hnRAC1. Comparative structural analysis indicates that backbone extension by β-residues increases subunit conformational heterogeneity, enabling tighter packing and formation of more thermostable fibrils. Examination of intra- and intermolecular contacts shows that enhanced π-π stacking, hydrophobic interactions, hydrogen bonds, and electrostatic interactions likely contribute to fibril stabilization. These results show that minimal backbone modifications can remodel amyloid architecture, offering a generalizable strategy for designing structurally diverse and robust peptide-based biomaterials.
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