靶向β-淀粉样蛋白聚集体荧光探针的合成与评价  

Preparation and evaluation of fluorescent probes for fluorescent detection of aggregated β-amyloid proteins

作　　者：李莹 李娜 张婷 程妍[1] LI Ying;LI Na;ZHANG Ting;CHENG Yan(Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry,West China School of Pharmacy,Sichuan University,Chengdu,Sichuan,610041 P.R.China)

机构地区：[1]四川大学华西药学院教育部药物靶向与给药系统重点实验室,四川成都610041

出　　处：《华西药学杂志》2021年第1期5-8,共4页West China Journal of Pharmaceutical Sciences

基　　金：国家自然科学基金资助项目(批准号:81402891)。

摘　　要：目的制备检测β-淀粉样蛋白(Aβ)聚集体的荧光探针。方法通过有机缩合反应制备3种探针,测定其紫外-可见吸收光谱和荧光光谱;测定探针与溶液中Aβ聚集体混合前后的荧光光谱;测定探针与转基因小鼠脑内Aβ聚集体混合后的荧光染色。结果通过核磁共振氢谱、核磁共振碳谱及高分辨率质谱确证了探针的结构。探针与溶液中Aβ聚集体混合后,荧光强度增强;其中,HN-3具有最显著的荧光增强效应(8.4倍);其亲和力最高,解离常数为137.0nmol·L-1。探针可荧光标记转基因鼠脑的Aβ聚集体。结论文中探针的制备方法简便、快捷,制备的3种探针均具有良好的亲和力和荧光信号,且与Aβ聚集体具有良好的亲和力;其中,HN-3的荧光增强效应最强,可用于溶液和生物组织中Aβ聚集状态的荧光增强检测。OBJECTIVE To develop fluorescent probes for fluorescent detection of aggregated β-amyloid proteins.METHODS The probes were prepared by organic condensation reaction. Absorption and fluorescence spectra were investigated. Fluorescence spectra of each probe in the presence of aggregated β-amyloid proteins in solutions was investigated.Fluorescent staining of each probe was investigated for aggregated β-amyloid proteins in the brain. RESULTS The probes were characterized by1 HNMR,13 CNMR and HRMS. All probes showed enhanced fluorescence intensity in the presence of Aβ1-42 aggregates. Among them,HN-3 showed the highest affinity of 137. 0 nmol·L-1 and fluorescence enhancement of 8. 4-fold. They also showed fluorescent labeling of aggregated β-amyloid proteins in APP/PS1 brain sections. CONCLSION The probes exhibits good affinity to aggregated β-amyloid proteins and favorable fluorescence turn-on upon mixing with Aβ1-42 aggregates.HN-3,with superior fluorescence turn-on effect,holds promise for simple and efficient fluorescence turn-on detection of aggregated β-amyloid proteins both in solutions and in tissue samples.

关 键 词：Β-淀粉样蛋白 Aβ聚集体 光学性质 荧光分析 荧光探针 荧光增强效应 结合亲和力 阿尔茨海默病 

分 类 号：R914[医药卫生—药物化学]