Inhibition of Aβ42 peptide aggregation by a binuclear ruthenium(II)-platinum(II) complex: Potential for multi-metal organometallics as anti-amyloid agents.
Inhibition of Aβ42 peptide aggregation by a binuclear ruthenium(II)-platinum(II) complex: Potential for multi-metal organometallics as anti-amyloid agents.
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DOI：
10.1021/cn100046m
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发表时间：
2010-08-23
影响因子：
5
通讯作者：
Rangachari, Vijayaraghavan
中科院分区：
文献类型：
--
作者：
Kumar, Amit;Moody, LaMaryet;Olaivar, Jason F.;Lewis, Nerissa A.;Khade, Rahul L.;Holder, Alvin A.;Zhang, Yong;Rangachari, Vijayaraghavan
多年来，为了开发治疗阿尔茨海默病(AD)的有效药物，人们对淀粉样蛋白(Aβ，Aβ)肽聚集抑制剂的设计进行了广泛的研究。最大的挑战似乎是在聚集的早期阶段抑制Aβ聚集，可能是在单体水平上，因为众所周知低聚物具有神经毒性。在这方面，利用Aβ的金属螯合特性来产生能够克服这一障碍的分子是有希望的。最近，一种含有PtII的金属络合物([Pt(Bps)Cl2])被报道能有效地抑制Aβ42的聚集和毒性。该复合体能够与多肽N末端的Aβ42结合，并引发构象变化，从而产生有效的抑制作用。在本报告中，我们产生了一个含有PtII和RuII的混合双核金属络合物，它在聚集的早期阶段抑制了Aβ42的聚集，并且似乎具有不同于先前报道的PtII络合物的相互作用模式，这表明第二金属中心具有重要的作用。这种“概念验证”化合物将通过修饰两个金属中心及其配体，帮助开发出更有效的抗Aβ聚集的分子，这将为抑制Aβ打开新的理论基础。
Design of inhibitors for amyloid-β (Aβ) peptide aggregation has been widely investigated over the years towards developing viable therapeutic agents for Alzheimer’s disease (AD). The biggest challenge seems to be inhibiting Aβ aggregation at the early stages of aggregation possibly at the monomeric level, as oligomers are known to be neurotoxic. In this regard, exploiting the metal chelating property of Aβ to generate molecules that can overcome this impediment presents some promise. Recently, one such metal complex containing PtII ([Pt(BPS)Cl2]) was reported to effectively inhibit Aβ42 aggregation and toxicity. This complex was able bind to Aβ42 at the N-terminal part of the peptide and triggered a conformational change resulting in effective inhibition. In the current report, we have generated a mixed-binuclear metal complex containing PtII and RuII that inhibited Aβ42 aggregation at an early stage of aggregation and seemed to have different modes of interaction than the previously reported PtII complex, suggesting an important role of the second metal center. This ‘proof-of-concept’ compound will help in developing more effective molecules against Aβ aggregation by modifying the two metal centers as well as their ligands, which will open doors to new rationale for Aβ inhibition.
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影响因子：
56.9
作者：
BUSH, AI;PETTINGELL, WH;TANZI, RE
通讯作者：
TANZI, RE
DOI：
10.1073/pnas.0702669104
发表时间：
2007-08-14
影响因子：
11.1
作者：
Dong, Jijun;Canfield, Jeffrey M.;Lynn, David G.
通讯作者：
Lynn, David G.
影响因子：
5.3
作者：
Kawarabayashi, T;Shoji, M;Younkin, SG
通讯作者：
Younkin, SG
影响因子：
4.2
作者：
Bush, AI
通讯作者：
Bush, AI
影响因子：
2.8
作者：
Cossi, M;Barone, V;Tomasi, J
通讯作者：
Tomasi, J