Ren Wenming, Xu Mingming, Liang Steven H, Xiang Huaijiang, Tang Li, Zhang Minkui, Ding Dejun, Li Xin, Zhang Haiyan, Hu Youhong
State Key Laborarory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Biosens Bioelectron. 2016 Jan 15;75:136-41. doi: 10.1016/j.bios.2015.08.030. Epub 2015 Aug 18.
Here we reported the development of the first photoinduced electron transfer (PeT) probe (1) to directly locate β-amyloid aggregates (Aβ plaques) in the brain without the need of post-washing procedures. The probe showed a high affinity for Aβ aggregates with a Kd value of 3.5nM. It is weakly emissive by itself with its fluorescence quenched by electron transfer from PeT donor to the excited fluorophore. But selective binding to Aβ plaques would attenuate the PeT process and restore the fluorescence, therefore facilitating the tracking of Aβ plaques. The probe is advantageous in that its fluorescence is environment-less-sensitive and no washing procedure is required to provide high contrast fluorescent signal when applied to stain brain tissues. As a proof of concept, its application has been exemplified by staining Aβ plaques in slices of brain tissue from double transgenic (APP/PS1) mice of Alzheimer's disease.
在此,我们报道了首个光诱导电子转移(PeT)探针(1)的研发,该探针可直接在大脑中定位β-淀粉样蛋白聚集体(Aβ斑块),无需后续洗涤步骤。该探针对Aβ聚集体具有高亲和力,解离常数(Kd)值为3.5 nM。其自身发射较弱,荧光因从PeT供体到激发荧光团的电子转移而猝灭。但与Aβ斑块的选择性结合会减弱PeT过程并恢复荧光,从而便于追踪Aβ斑块。该探针的优势在于其荧光对环境不敏感,应用于脑组织染色时无需洗涤步骤即可提供高对比度荧光信号。作为概念验证,已通过对阿尔茨海默病双转基因(APP/PS1)小鼠脑组织切片中的Aβ斑块进行染色来例证其应用。