Mechanism-based molecular design of highly selective fluorescence probes for nitrative stress
Mechanism-based molecular design of highly selective fluorescence probes for nitrative stress
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DOI：
10.1021/ja061972v
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发表时间：
2006-08-23
影响因子：
15
通讯作者：
Nagano, Tetsuo
中科院分区：
文献类型：
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作者：
Ueno, Tasuku;Urano, Yasuteru;Nagano, Tetsuo
硝化应激与包括神经退行性疾病在内的多种致病过程有关，但目前还没有实用的荧光探针可以高选择性地监测硝化应激的产生。为了设计合适的荧光探针，我们首先关注硝基的荧光猝灭机制，硝基被认为是荧光染料的独特猝灭剂。我们发现，硝基基团为基础的荧光猝灭可以解释在电子转移过程中，从激发的荧光团的缺电子的芳香族硝基部分。通过利用这一结果，我们成功地开发了新的荧光探针，NiSPYs，它可以选择性地监测基于芳香族硝化的硝化应力的产生。NiSPYs在与硝化剂（包括过氧亚硝酸根）反应时显示出强烈的荧光增强，但在其他活性氧物质的存在下显示出很少或没有荧光增强。NiSPYs应该是潜在有用的工具，研究硝化应激在各种生物学应用中的作用。
Nitrative stress is implicated in various pathogenic processes, including neurodegenerative disorders, but there is no practical fluorescence probe which can monitor the generation of nitrative stress with high selectivity. To design a suitable fluorescence probe, we have first focused on the fluorescence quenching mechanism of the nitro group, which has been believed to be a unique quencher of fluorescent dyes. We found that nitro group-based fluorescence quenching could be explained in terms of an electron transfer process, from the excited fluorophore to the electron-deficient aromatic nitro moiety. By utilizing this result, we succeeded in developing novel fluorogenic probes, NiSPYs, which can selectively monitor the generation of nitrative stress based on aromatic nitration. NiSPYs showed strong fluorescence enhancement upon the reaction with nitrating agents, including peroxynitrite, but showed little or no fluorescence augmentation in the presence of other reactive oxygen species. NiSPYs should be potentially useful as tools to study the role of nitrative stress in various biological applications.