用于Aβ标记的新型近红外荧光染料BPAD-2的制备与生物学评价

以邻羟基苯乙酮为初始原料,通过缩合反应合成了2-{2-2-(4-羟基苯基)乙烯基]苯并吡喃-4-}-丙二腈(BPAD-2),并通过1 H-NMR与MS确认结构;考察所制备探针的荧光光谱;通过荧光染色考察探针的Aβ结合标记;通过荧光成像考察探针的血脑屏障通过能力.结果表明BPAD-2的最大发射波长为658nm;BPAD-2荧光标记的Aβ呈亮红色;BPAD-2尾静脉注入正常小鼠后脑内显示荧光信号,10min内荧光强度达到最高,随着时间延长荧光强度逐渐减弱.说明苯并吡喃结构的BPAD-2具有近红外荧光性质,并显示良好的Aβ荧光标记和血脑屏障通过能力.

Synthesis and evaluation of near infrared fluorescent dye BPAD-2 for β-amyloid plaques

OBJECTIVE We synthesized a benzopyrane derivative BPAD-2 with push-pull electronic structure, and assessed its fluorescence properties, labelling ability for beta-amyloid plaques, and blood-brain barrier penetrating ability. METHODS BPAD-2 was synthesized by condensation reaction with 1-(2-hydroxy-phenyl)-ethanone as the primary reagent, and confirmed by 1H-NMR and MS. Fluorescence spectra were observed; fluorescence staining was performed to evaluate labelling ability for beta-amyloid plaques; fluorescent imaging was performed to evaluate blood-brain barrier penetrating ability. RESULTS The emission maximum of BPAD-2 in PBS was at 658 nm; BPAD-2 showed bright red labelling of beta-amyloid plaques; BPAD-2 penetrated the blood-brain barrier and peaked at 10 min postinjection and showed reasonable washout from the brain. CONCLSION BPAD-2 showed specific labelling of beta-amyloid plaques and had good blood-brain barrier penetrating ability.