Using a build-and-click approach for producing structural and functional diversity in DNA-targeted hybrid anticancer agents.
Using a build-and-click approach for producing structural and functional diversity in DNA-targeted hybrid anticancer agents.
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DOI：
10.1021/jm301278c
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发表时间：
2012-11-26
影响因子：
7.3
通讯作者：
Bierbach, Ulrich
中科院分区：
文献类型：
--
作者：
Ding, Song;Qiao, Xin;Kucera, Gregory L.;Bierbach, Ulrich
建立了一种基于金属介导的胺腈加成（一种“点击”化学形式）的功能化dna靶向含铂杂化抗癌药物的高效筛选方法。该研究的目标是生成铂-吖啶制剂，用于靶向和多功能治疗中的细胞毒性“弹头”。这是通过在吖啶连接体部分引入羟基、羧酸和叠氮化官能团以及改变附着在铂上的非离去基团来实现的。该分析基于6种铂腈配合物与10种吖啶衍生物之间的微尺度反应，产生了60种铂吖啶衍生物的小文库。通过自动在线高效液相色谱-电喷雾质谱（LC-ESMS）分析对反应进行监测，对产物混合物进行定量分析，并使用非放射性细胞增殖试验进行细胞活力筛选。新的预筛选方法被证明是建立结构-活性关系和鉴定目标化合物的有力工具。
An efficient screening method was developed for functionalized DNA-targeted platinum-containing hybrid anticancer agents based on metal-mediated amine-to-nitrile addition, a form of “click” chemistry. The goal of the study was to generate platinum–acridine agents for their use as cytotoxic “warheads” in targeted and multifunctional therapies. This was achieved by introducing hydroxyl, carboxylic acid, and azide functionalities in the acridine linker moiety and by varying the nonleaving groups attached to platinum. The assay, which was based on microscale reactions between 6 platinum–nitrile complexes and 10 acridine derivatives, yielded a small library of 60 platinum–acridines. Reactions were monitored and product mixtures were quantitatively analyzed by automated in-line high-performance liquid chromatography– electrospray mass spectrometry (LC-ESMS) analysis and subjected to cell viability screening using a non-radioactive cell proliferation assay. The new prescreening methodology proves to be a powerful tool for establishing structure–activity relationships and for identifying target compounds.
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影响因子：
7.3
作者：
Ma Z;Choudhury JR;Wright MW;Day CS;Saluta G;Kucera GL;Bierbach U
通讯作者：
Bierbach U
影响因子：
4.2
作者：
Smyre, Christopher L.;Saluta, Gilda;Kute, Timothy E.;Kucera, Gregory L.;Bierbach, Ulrich
通讯作者：
Bierbach, Ulrich
影响因子：
4.2
作者：
Graham, Leigh A.;Wilson, Gary M.;West, Tiffany K.;Day, Cynthia S.;Kucera, Gregory L.;Bierbach, Ulrich
通讯作者：
Bierbach, Ulrich
影响因子：
14.8
作者：
Srinivasan, Rajavel;Li, Junqi;Yao, Shao Q.
通讯作者：
Yao, Shao Q.
DOI：
10.1073/pnas.0707090104
发表时间：
2007-10-23
影响因子：
11.1
作者：
Baskin, Jeremy M.;Prescher, Jennifer A.;Bertozzi, Carolyn R.
通讯作者：
Bertozzi, Carolyn R.