2. Academic Validation
  3. Design and synthesis of β-strand-fixed peptides inhibiting aggregation of amyloid β-protein

Design and synthesis of β-strand-fixed peptides inhibiting aggregation of amyloid β-protein

  • Bioorg Med Chem. 2020 Sep 15;28(18):115676. doi: 10.1016/j.bmc.2020.115676.
Fumiya Tanaka 1,  Kana Shibata 1,  Yoko Monobe 2,  Ken-Ichi Akagi 2,  Yuichi Masuda 3
Affiliations

Affiliations

  • 1 Graduate School of Bioresources, Mie University, 1577 Kurimamachiya-cho, Tsu 514-8507, Japan.
  • 2 National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan.
  • 3 Graduate School of Bioresources, Mie University, 1577 Kurimamachiya-cho, Tsu 514-8507, Japan. Electronic address: [email protected].
PMID: 32828432 DOI: 10.1016/j.bmc.2020.115676
Abstract

Aggregation of 42-residue amyloid β-protein (Aβ42) can be prevented by β-sheet breaker Peptides (BSBps) homologous to LVFFA residues, which are included in a β-sheet region of Aβ42 aggregates. To enhance the affinity of BSBps to the Aβ42 aggregates, we designed and synthesized β-strand-fixed Peptides (BSFps) whose side chains were cross-linked by ring closing metathesis. Conformation analysis verified that the designed Peptides could be fixed in β-strand conformation. Among the synthesized pentapeptides, 1 and 12, whose side chains of 2nd and 4th residues were cross-linked, significantly inhibited the aggregation of Aβ42. This suggested that β-strand-fixation of BSBps could enhance their inhibitory activity against the Aβ42 aggregation. However, pentapeptides 1 and 12 had little effect on morphology of Aβ42 aggregates (fibrils) and neurotoxicity of Aβ42 against SH-SY5Y cells.

Keywords

Amyloid β-protein; Conformation analysis; Conformation fixation; β-Sheet breaker peptide; β-Strand mimetics.

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