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Updated: Jun 22, 2026

Photo-Induced Cross-Linking of Unmodified Proteins PICUP Applied to Amyloidogenic Peptides
Published on: January 12, 2009
Screening π-Extended Ruthenium(II) Complexes for the Photoinduced Oxidative Modulation of Amyloid-β Peptide
Grace Leech1, Isabella Bayly1, Alisher Talgatov2
1Department of Chemistry, Simon Fraser University, Burnaby, BC V5A-1S6, Canada.
None:
Controlling the aggregation of amyloid-β (Aβ) peptides offers a promising strategy to mitigate Alzheimer's disease (AD). Herein, we introduce a series of photoactivatable Ru(II) complexes (Ru1-8) designed to efficiently generate singlet oxygen (1O2) and subsequently oxidatively modify the Aβ peptide. Upon light activation, these complexes rapidly direct Aβ1-42 aggregation toward high molecular weight amorphous species, with Ru1 demonstrating the most pronounced effect. Transmission electron microscopy (TEM) revealed that the amorphous aggregates formed immediately and persist over time. Complementary assays, including bicinchoninic acid (BCA) quantification and Western blotting, demonstrated rapid photoinduced aggregation and a decrease of soluble peptide upon photoactivation, while proteinase-K digestion showed that the resulting amorphous species are more susceptible to proteolysis in comparison to canonical fibrils. Control experiments under anaerobic conditions and in the presence of an 1O2 scavenger suggest that these effects are oxygen-dependent. Notably, photoactivation of Ru1 in the presence of preformed fibrils results in a morphology change to degradable amorphous aggregates, providing both preventive and disruptive activity. Together, these findings establish photoactivatable Ru1 as a light-controlled chemical tool capable of redirecting Aβ aggregation, enhancing aggregate protease degradation, and offering a versatile platform for therapeutic exploration.
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