Reactive Amphiphilic Conjugated Polymers for Inhibiting Amyloid β Assembly

Protein misfolding and aberrant aggregations are associated with multiple prevalent and intractable diseases. Inhibition of the amyloid assembly is a promising strategy for the treatment of amyloidoses. However, present effective inhibitors binding to target proteins are based on non‐covalent interactions, which are intrinsically weak and susceptible. Here, we designed and synthesized a reactive conjugated polymer, poly (p‐phenylene vinylene) derivative functionalized with p‐nitrophenyl active ester (PPV‐NP) that could inhibit the assembly of amyloid proteins, degrade preformed fibrils and cut down the cytotoxicity of amyloid aggregations in living cells through combining hydrophobic interactions with irreversible covalent linkage. PPV‐NP also exhibited excellent capacity to eliminate Aβ plaques in brain slices in ex vivo assays. This work represents an innovative attempt to inhibit protein pathogenic aggregates, which may offer insights into the development of therapeutic strategies for amyloidosis.

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