Reactivity of diphenylpropynone derivatives toward metal-associated amyloid-β species.
Reactivity of diphenylpropynone derivatives toward metal-associated amyloid-β species.
复制标题
DOI：
10.1021/ic302084g
复制
发表时间：
2012-12-03
影响因子：
4.6
通讯作者：
Lim MH
中科院分区：
文献类型：
--
作者：
Pithadia AS;Kochi A;Soper MT;Beck MW;Liu Y;Lee S;DeToma AS;Ruotolo BT;Lim MH
在阿尔茨海默病（AD）中，金属相关淀粉样蛋白-β（金属-A β）物质被认为与神经毒性有关;然而，它们在疾病发展中的作用仍不清楚。为了阐明这一方面，化学试剂已被开发为靶向金属-A β物质、调节金属与Aβ之间的相互作用并随后改变金属-A β反应性的有价值的工具。在此，我们报告的设计，制备，表征和反应性的两个二苯基丙炔酮衍生物（DPP 1和DPP 2）的金属螯合和Aβ相互作用（双功能性）的结构部分组成。这些化合物与金属离子和Aβ物质的相互作用通过UV-Vis、质谱和对接研究得到证实。通过凝胶电泳和透射电子显微镜（TEM）研究和监测这些双功能分子对体外无金属和金属诱导的Aβ聚集的控制作用。DPP 1和DPP 2对金属-A β物质的反应性均高于无金属Aβ物质。特别是，含有二甲氨基的DPP 2与金属-A β物质的反应性比DPP 1更高，表明结构-反应性关系。总的来说，我们的研究提出了一种新的双功能支架，可用于开发化学试剂，用于研究AD中的金属-A β物质。
In Alzheimer’s disease (AD), metal-associated amyloid-β (metal–Aβ) species have been suggested to be involved in neurotoxicity; however, their role in disease development is still unclear. To elucidate this aspect, chemical reagents have been developed as valuable tools for targeting metal–Aβ species, modulating the interaction between the metal and Aβ, and subsequently altering metal–Aβ reactivity. Herein, we report the design, preparation, characterization, and reactivity of two diphenylpropynone derivatives (DPP1 and DPP2) composed of structural moieties for metal chelation and Aβ interaction (bifunctionality). The interactions of these compounds with metal ions and Aβ species were confirmed by UV-Vis, mass spectrometry, and docking studies. The effects of these bifunctional molecules on the control of in vitro metal-free and metal-induced Aβ aggregation were investigated and monitored by gel electrophoresis and transmission electron microscopy (TEM). Both DPP1 and DPP2 showed reactivity toward metal–Aβ species over metal-free Aβ species to different extents. In particular, DPP2, which contains a dimethylamino group, exhibited greater reactivity with metal–Aβ species than DPP1, suggesting a structure-reactivity relationship. Overall, our studies present a new bifunctional scaffold that could be utilized to develop chemical reagents for investigating metal–Aβ species in AD.
登录
查看更多内容
影响因子：
20.6
作者：
Alderighi, L;Gans, P;Vacca, A
通讯作者：
Vacca, A
影响因子：
46.2
作者：
DeToma AS;Salamekh S;Ramamoorthy A;Lim MH
通讯作者：
Lim MH
影响因子：
--
作者：
Braymer JJ;Detoma AS;Choi JS;Ko KS;Lim MH
通讯作者：
Lim MH
DOI：
10.1039/c2dt12207c
发表时间：
2012-06-07
期刊：
Dalton transactions (Cambridge, England : 2003)
影响因子：
--
作者：
He X;Park HM;Hyung SJ;DeToma AS;Kim C;Ruotolo BT;Lim MH
通讯作者：
Lim MH
DOI：
10.1039/c2mt20052j
发表时间：
2012-08
期刊：
Metallomics : integrated biometal science
影响因子：
--
作者：
Bourassa MW;Miller LM
通讯作者：
Miller LM