Aβ斑块靶向近红外荧光探针的合成及评价
Synthesis and evaluation of near-infrared fluorescent probes for β-amyloid plaques
作者：张婷;张志荣;程妍;
Author：
收稿日期： 年卷（期）页码：2019,34(04):-320-324
期刊名称：华西药学杂志
Journal Name：WEST CHINA JOURNAL OF PHARMACEUTICAL SCIENCES
关键字：阿尔兹海默症;Aβ斑块;近红外荧光探针;成像;喹啉类;体外;结合能力;染色;光学性质;蛋白结合饱和实验;靶向性;APP/PS1转基因小鼠脑切片
Key words：
基金项目：国家自然科学基金资助项目(批准号:81402891)
中文摘要
目的制备近红外荧光探针ZZN-4、ZZN-6,并考察其光学性质及与Aβ_(1-42)聚集体、APP/PS1转基因小鼠脑内Aβ斑块的结合能力。方法以2-喹啉甲醛及4-(二甲氨基)肉桂醛为原料,通过缩合反应制备探针ZZN-4、ZZN-6,并通过~1HNMR、~(13)CNMR、MS确认结构。考察所制备探针的紫外吸收及与蛋白结合前、后荧光性质的变化;通过蛋白结合饱和实验测定探针与Aβ1-42聚集体结合的解离常数(K_d);对APP/PS1转基因小鼠脑切片进行体外荧光染色,考察其与Aβ斑块的结合能力。结果 ZZN-4、ZZN-6与Aβ_(1-42)聚集体结合后,荧光最大发射波长均发生蓝移(分别为635、629 nm),但仍处于近红外区;荧光强度分别增强52. 4、15. 9倍;其中,ZZN-4与Aβ1-42聚集体结合的Kd为6. 89nmol·L~(-1)。APP/PS1转基因鼠脑切片的荧光染色结果表明:ZZN-4可与Aβ斑块特异性结合。结论荧光探针ZZN-4在体外表现出对Aβ_(1-42)聚集体的高亲和力,并对脑切片Aβ斑块具有较好的靶向性,有潜力成为阿尔兹海默症患者脑内Aβ斑块的近红外荧光成像剂。
参考文献
[1] Rajasekhar K,Narayanaswamy N,Murugan N,et al. A high affinity red fluorescence and colorimetric probe for amyloidβaggregates[J]. Sci Rep,2016,6:23668.
[2] Mathis CA,Wang Y,Holt DP,et al. Synthesis and evaluation of11C-labeled 6-substituted 2-arylbenzothiazoles as amyloid imaging agents[J]. J Med Chem,2003,46(13):2740-2754.
[3]邹肇娥,王化远,唐元清.荧光探针的应用[J].华西药学杂志,1991,6(4):223-228.
[4] Staderini M,Martin MA,Bolognesic ML,et al. Imaging ofβ-amyloid plaques by near infrared fluorescent tracers:A new frontier for chemical neuroscience[J]. Chem Soc Rev,2015,44(7):1807-1819.
[5] Ran C,Xu X,Raymond SB,et al. Design,synthesis,and testing of difluoroboron derivatized curcumins as near infrared probes for in vivo detection of amyloid-βdeposits[J]. J Am Chem Soc,2009,131(42):15257-15261.
[6] Cui M,Ono M,Watanabe H,et al. Smart near-infrared fluorescence probes with donor-acceptor structure for in vivo detection of β-amyloid deposits[J]. J Am Chem Soc,2014,136(9):3388-3394.
[7] Fu HL,Cui MC,Tu PY,et al. Evaluation of molecules based on the electron donor-acceptor architecture as near-infraredβ-amyloid-targeting probes[J]. Chem Comm,2014,50(80):11875-11878.
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