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
复制标题
抑制β淀粉样蛋白聚集的β链固定肽的设计与合成
DOI：
10.1016/j.bmc.2020.115676
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发表时间：
2020
影响因子：
3.5
通讯作者：
Masuda Yuichi
中科院分区：
文献类型：
--
作者：
Tanaka Fumiya;Shibata Kana;Monobe Yoko;Akagi Ken-ichi;Masuda Yuichi
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,1and12, 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, pentapeptides1and12had little effect on morphology of Aβ42 aggregates (fibrils) and neurotoxicity of Aβ42 against SH-SY5Y cells.
