title: Antiamyloidogenic Activity of Aβ42-Binding Peptoid in Modulating Amyloid Oligomerization.
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.
authors.affiliation: 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.
authors.forename: Zijian
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: 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.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhu
authors.affiliation: 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.
authors.forename: Haiyun
authors.initials: H
authors.lastname: Li
authors.affiliation: State Key Laboratory of Tribology, Department of Mechanical Engineering, Tsinghua University, Beijing, 100084, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Cheng
authors.affiliation: 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.
authors.forename: Jiaxi
authors.initials: J
authors.lastname: Peng
authors.affiliation: 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.
authors.forename: Yudan
authors.initials: Y
authors.lastname: Yin
authors.affiliation: 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.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Hu
authors.affiliation: 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.
authors.forename: Yanlian
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000682:Amyloid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000187:drug effects; D002942:Circular Dichroism; D006801:Humans; D019151:Peptide Library; D034444:Peptoids / Q000494:pharmacology*; D011487:Protein Conformation; D055503:Protein Multimerization
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D019151:Peptide Library; D034444:Peptoids
keywords: aggregation; amyloid oligomerization; antiamyloidogenic; inhibitor; peptoids