Excited-State Intramolecular Hydrogen Transfer of Compact Molecules Controls Amyloid Aggregation Profiles
Mannkyu Hong, Mingeun Kim, Jiwon Yoon, Seung‐Hee Lee, Mu‐Hyun Baik, Mi Hee Lim
Abstract
backbone and the consequent intramolecular hydrogen transfer can facilitate the energy transfer to triplet oxygen. Biochemical and biophysical investigations confirmed that these photoactive chemical reagents can oxidatively vary both metal-free amyloid-β (Aβ) and metal-bound Aβ, thereby redirecting their on-pathway aggregation into off-pathway as well as disassembling their preformed aggregates. Moreover, the in vivo histochemical analysis of Aβ species produced upon photoactivation of the most promising candidate demonstrated that they do not aggregate into oligomeric or fibrillar aggregates in the brain. Overall, our combined computational and experimental studies validate a light-based approach for designing small molecules, with minimum structural complexity, as chemical reagents targeting and controlling amyloidogenic peptides associated with neurodegenerative disorders.