Fibril Paint: a class of amyloid-targeting peptides

Abstract

Neurodegenerative diseases, such as Alzheimer’s Disease, Parkinson’s Disease and Huntington’s Disease, are characterised by accumulation of amyloid fibrils, which remain incurable. It is of great importance to develop early-diagnosis approaches as well as disease-modifying therapies. Recently, we discovered the FibrilPaint1 peptide, a specific amyloid binder that can serve for fibril diagnosis. Here we introduce a class of FibrilPaint1 derivatives that bind to protein fibrils. The modifications include variation of the charge, termini and order of residues. As a result, we generated a class of peptides with general fibril-binding properties and with the potential for further adaptation, such as linkage to multiple dyes, optimisation for specific protein and aggregate strains, or adaptation for targeted protein degradation strategies. Thus, Fibril Paint peptides are a class of promising leads for targeting amyloid fibrils for diagnostic and therapeutic purposes.