Premium
Antiamyloidogenic Activity of Aβ42‐Binding Peptoid in Modulating Amyloid Oligomerization
Author(s) -
Zhao Zijian,
Zhu Ling,
Li Haiyun,
Cheng Peng,
Peng Jiaxi,
Yin Yudan,
Yang Yang,
Wang Chen,
Hu Zhiyuan,
Yang Yanlian
Publication year - 2017
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201602857
Subject(s) - peptoid , chemistry , cytotoxicity , biophysics , in vitro , fibril , amyloid (mycology) , surface plasmon resonance , membrane permeability , biochemistry , microbiology and biotechnology , membrane , peptide , nanotechnology , biology , materials science , nanoparticle , inorganic chemistry
The oligomerization and aggregation of amyloid β (Aβ) play central role in the pathogenesis of Alzheimer's disease (AD). Molecular binding agents for modulating the formation of Aβ oligomers and fibrils have promising application potential in AD therapies. By screening a peptoid library using surface plasmon resonance imaging, amyloid inhibitory peptoid 1 (AIP1) that has high affinity to Aβ42 is identified. AIP1 is demonstrated to inhibit Aβ42 oligomerization and fibrillation and to rescue Aβ42‐induced cytotoxicity through decreasing the content of Aβ42 oligomers that is related to cell membrane permeability. Molecular docking suggests that the binding sites of AIP1 may be at the N‐terminus of Aβ42. The blood‐brain barrier (BBB) permeability of AIP1 using an in vitro BBB model is also revealed. This work provides a strategy for the design and development of peptoid‐based antiamyloidogenic agents. The obtained amyloid inhibitory peptoid shows prospects in the therapeutic application in AD.