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Small. 2017 Jan;13(1). doi: 10.1002/smll.201602857. Epub 2016 Oct 7.

Antiamyloidogenic Activity of Aβ42-Binding Peptoid in Modulating Amyloid Oligomerization.

Author information

1
CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory of Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, China.
2
State Key Laboratory of Tribology, Department of Mechanical Engineering, Tsinghua University, Beijing, 100084, China.
3
Beijing National Laboratory for Molecular Sciences, MOE Key Laboratory of Polymer Chemistry and Physics, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.

Abstract

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.

KEYWORDS:

aggregation; amyloid oligomerization; antiamyloidogenic; inhibitor; peptoids

PMID:
27714968
DOI:
10.1002/smll.201602857
[Indexed for MEDLINE]

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