Antiamyloidogenic Activity Of A Beta 42-Binding Peptoid In Modulating Amyloid Oligomerization

The oligomerization and aggregation of amyloid beta (A beta) play central role in the pathogenesis of Alzheimer's disease (AD). Molecular binding agents for modulating the formation of A beta 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 A beta 42 is identified. AIP1 is demonstrated to inhibit A beta 42 oligomerization and fibrillation and to rescue A beta 42-induced cytotoxicity through decreasing the content of A beta 42 oligomers that is related to cell membrane permeability. Molecular docking suggests that the binding sites of AIP1 may be at the N-terminus of A beta 42. 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.