Authors
Júlia Aragonès Pedrola, Françoise A Dekker, Katrin Guttmann, Litske M van Leeuwen, Shalini Singh, Guy Mayer, Tommaso Garfagnini, Assaf Friedler, Stefan G D Rüdiger
Published in
Chemistry (Weinheim an der Bergstrasse, Germany). Pages e71539. Aug 05, 2026. Epub Aug 05, 2026.
Abstract
Amyloid fibrils are a common pathological hallmark in multiple neurodegenerative diseases, yet molecular tools to recognize and manipulate them remain scarce. We report FibrilPaints, a family of modular peptides designed for amyloid binding and adaptable chemical functionality. The degenerative amyloid-targeting unit of FibrilPaints, W5P4H3R2, has a high content of π-stacking and aromatic side chains. Systematic sequence variation, altering charge, termini, and residue order, revealed the importance of the composition of the amyloid-targeting unit for high-affinity binding across Tau and Huntingtin fibrils. Importantly, sequence changes outside this unit do not preclude fibril binding, which permits attachment of fluorophores or E3-recruiting motifs for targeted protein degradation. This work establishes FibrilPaint as a modular peptide system for binding Tau and Huntingtin amyloid fibrils, with potential for broader detection and modulation applications.
PMID:
42554508
Bibliographic data and abstract were imported from PubMed on 05 Aug 2026.
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