title: Synthesis and evaluation of styrylpyran fluorophores for noninvasive detection of cerebral β-amyloid deposits.
abstract: The development of amyloid-specific fluorophores allows the visualization of cerebral β-amyloid deposits using optical imaging technology. In the present study, a series of smart styrylpyran fluorophores with compact donor-acceptor architecture were designed and evaluated for noninvasive detection of cerebral β-amyloid deposits. Spectral behavior of the fluorophores changed significantly (optical turn-on) upon binding to β-amyloid aggregates. Computational studies were conducted to correlate the experimental Kd values with calculated binding energies, speculating the relationship between fluorophore structure and β-amyloid affinity. In vivo studies demonstrated that PAD-2 could discriminate APP/PS1 transgenic mice from wild type controls, with specific labeling of cerebral β-amyloid deposits confirmed by ex vivo observation. Collectively, these styrylpyran fluorophores could provide a new scaffold for the development of optical imaging probes targeting cerebral β-amyloid deposits.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Bi-yue
authors.initials: BY
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. Electronic address: yancheng@scu.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
authors.forename: Guo-bo
authors.initials: GB
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
authors.forename: Sheng-yong
authors.initials: SY
authors.lastname: Yang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Zhi-rong
authors.initials: ZR
authors.lastname: Zhang
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D020816:Amino Acid Motifs; D000682:Amyloid / Q000378:metabolism / Q000648:ultrastructure*; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D061848:Optical Imaging; D058225:Plaque, Amyloid / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011714:Pyrans / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013343:Styrenes / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000378:metabolism
chemical_list: D000682:Amyloid; D005456:Fluorescent Dyes; D011714:Pyrans; D013343:Styrenes
keywords: Fluorophore; Optical imaging; Styrylpyran; β-Amyloid deposits