Reactive Amphiphilic Conjugated Polymers for Inhibiting Amyloid β Assembly

Angewandte Chemie
Han SunShu Wang

Abstract

Protein misfolding and aberrant aggregations are associated with multiple prevalent and intractable diseases. Inhibition of amyloid assembly is a promising strategy for the treatment of amyloidosis. Reported here is the design and synthesis of a reactive conjugated polymer, a poly(p-phenylene vinylene) derivative, functionalized with p-nitrophenyl esters (PPV-NP) and it inhibits the assembly of amyloid proteins, degrades preformed fibrils, and reduces the cytotoxicity of amyloid aggregations in living cells. PPV-NP is attached to the proteins through hydrophobic interactions and irreversible covalent linkage. PPV-NP also exhibited the capacity to eliminate Aβ plaques in brain slices in ex vivo assays. This work represents an innovative attempt to inhibit protein pathogenic aggregates, and may offer insights into the development of therapeutic strategies for amyloidosis.

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Citations

Oct 22, 2019·Macromolecular Rapid Communications·Zhanna EvgrafovaWolfgang H Binder
Jul 9, 2020·Nanoscale·Nicholas AndrikopoulosPu Chun Ke
Oct 20, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Hao GengChengfen Xing
Jun 30, 2019·ACS Applied Materials & Interfaces·Han SunShu Wang
Aug 21, 2020·ACS Chemical Neuroscience·Lakshmi Priya DattaThimmaiah Govindaraju
Jan 8, 2022·Angewandte Chemie·Man-Di WangHao Wang

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