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Peer-reviewedCC BY-NC-ND 4.0Chemistry (Weinheim an Der Bergstrasse, Germany)

Fibrilpaint: A Class of Amyloid‐Targeting Peptides

  • Júlia Aragonès Pedrola1,2,3
  • Françoise A. Dekker1,2,3
  • Katrin Guttmann3
  • Litske M. van Leeuwen2,3
  • Shalini Singh4
  • Guy Mayer4
  • Tommaso Garfagnini4
  • Assaf Friedler4
  • Stefan G. D. Rüdiger1,2,3
4 affiliations
  1. 1Cellular Protein Chemistry, Bijvoet Center for Biomolecular Research Utrecht University Utrecht The Netherlands
  2. 2Science for Life Utrecht University Utrecht The Netherlands
  3. 3Protein Chemistry of Disease, Department of Chemistry Utrecht University Utrecht The Netherlands
  4. 4Institute of Chemistry, Edmond J. Safra Campus at Givat Ram The Hebrew University of Jerusalem Jerusalem Israel
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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.

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Cite

BibTeXRIS
BibTeX
@article{pedrola2026fibrilpaint,
  title = {{Fibrilpaint: A Class of Amyloid‐Targeting Peptides}},
  author = {Júlia Aragonès Pedrola and Françoise A. Dekker and Katrin Guttmann and Litske M. van Leeuwen and Shalini Singh and Guy Mayer and Tommaso Garfagnini and Assaf Friedler and Stefan G. D. Rüdiger},
  journal = {Chemistry (Weinheim an Der Bergstrasse, Germany)},
  year = {2026},
  month = aug,
  doi = {10.1002/chem.71539},
  url = {https://doi.org/10.1002/chem.71539},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Fibrilpaint: A Class of Amyloid‐Targeting Peptides
AU  - Júlia Aragonès Pedrola
AU  - Françoise A. Dekker
AU  - Katrin Guttmann
AU  - Litske M. van Leeuwen
AU  - Shalini Singh
AU  - Guy Mayer
AU  - Tommaso Garfagnini
AU  - Assaf Friedler
AU  - Stefan G. D. Rüdiger
PY  - 2026
DA  - 2026/08/05
JO  - Chemistry (Weinheim an Der Bergstrasse, Germany)
DO  - 10.1002/chem.71539
UR  - https://doi.org/10.1002/chem.71539
AB  - 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.
SN  - 0947-6539
SN  - 1521-3765
ER  -