Design, synthesis, and testing of difluoroboron-derivatized curcumins as near-infrared probes for in vivo detection of amyloid-beta deposits.
Design, synthesis, and testing of difluoroboron-derivatized curcumins as near-infrared probes for in vivo detection of amyloid-beta deposits.
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DOI：
10.1021/ja9047043
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发表时间：
2009-10-28
影响因子：
15
通讯作者：
Moore, Anna
中科院分区：
文献类型：
--
作者：
Ran, Chongzhao;Xu, Xiaoyin;Raymond, Scott B.;Ferrara, Brian J.;Neal, Krista;Bacskai, Brian J.;Medarova, Zdravka;Moore, Anna
β淀粉样蛋白（Aβ）沉积已被确定为阿尔茨海默病（AD）进展的关键参与者。最近的证据表明，这些沉积物可能先于并诱导神经元萎缩。因此，能够在观察到临床症状之前监测病理的方法将有利于早期AD检测。在这里，我们报告的设计，合成和测试的姜黄素衍生的近红外（NIR）探针CRANAD-2。在与Aβ聚集体相互作用后，CRANAD-2经历了一系列变化，包括70倍的荧光强度增加，90 nm蓝移（从805 nm到715 nm）和量子产率的大幅增加。此外，该探针还显示出对Aβ聚集体的高亲和力（Kd = 38.0 nM）、合理的Log P值（Log P = 3）、在血清中相当稳定以及与白蛋白的弱相互作用。静脉注射该探针后，19月龄Tg 2576小鼠在相同时间段内表现出比对照小鼠显著更高的相对信号。总之，CRANAD-2符合用于体外和体内Aβ斑块检测的NIR造影剂的所有要求。我们的数据指向通过CRANAD-2的NIR成像监测疾病进展的可行性。此外，我们相信，我们的探针可以潜在地用作药物筛选的工具。
Amyloid-β (Aβ) deposits have been identified as key players in the progression of Alzheimer’s disease (AD). Recent evidence indicates that the deposits probably precede and induce the neuronal atrophy. Therefore, methods that enable monitoring the pathology before clinical symptoms are observed would be beneficial for the early AD detection. Here, we report the design, synthesis, and testing of a curcumin derivatized near infrared (NIR) probe CRANAD-2. Upon interacting with Aβ aggregates, CRANAD-2 undergoes a range of changes, which include a 70-fold fluorescence intensity increase, a 90 nm blue-shift (from 805 nm to 715 nm), and a large increase in quantum yield. Moreover, this probe also shows a high affinity for Aβ aggregates (Kd = 38.0 nM), a reasonable Log P value (Log P = 3), considerable stability in serum and a weak interaction with albumin. After intravenous injection of this probe, 19-month old Tg2576 mice exhibited significantly higher relative signal than that of the control mice over the same period of time. In summary, CRANAD-2 meets all the requirements for a NIR contrast agent for the detection of Aβ plaques both in vitro and in vivo. Our data point towards the feasibility of monitoring the progress of the disease by NIR imaging with CRANAD-2. In addition, we believe that our probe could be potentially used as a tool for drug screening.
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影响因子：
4.3
作者：
Cogné-Laage, E;Allemand, JF;Jullien, L
通讯作者：
Jullien, L
影响因子：
16.6
作者：
Li, QA;Lee, JS;Chang, YT
通讯作者：
Chang, YT
影响因子：
16.6
作者：
Nesterov, EE;Skoch, J;Swager, TM
通讯作者：
Swager, TM
DOI：
10.1007/s00259-007-0708-7
发表时间：
2008-03-01
影响因子：
9.1
作者：
Raymond, Scott B.;Skoch, Jesse;Bacskai, Brian J.
通讯作者：
Bacskai, Brian J.
DOI：
10.1093/jnen/62.2.137
发表时间：
2003-02-01
影响因子：
3.2
作者：
D'Amore, JD;Kajdasz, ST;Hyman, BT
通讯作者：
Hyman, BT