Enzymatic reduction-resistant nitroxyl spin probes with spirocyclohexyl rings
Enzymatic reduction-resistant nitroxyl spin probes with spirocyclohexyl rings
复制标题
DOI：
10.1080/10715760701449302
复制
发表时间：
2007-01-01
影响因子：
3.3
通讯作者：
Takeshita, Keizo
中科院分区：
文献类型：
--
作者：
Okazaki, Shoko;Mannan, Md Abdul;Takeshita, Keizo
为了抑制自旋探针中氮氧基的酶还原，本研究设计了两种新型的氮氧基探针，分别为4-羟基和4-氧-哌啶-N-氧基(分别为羟基-DICPO和氧代-DICPO)。与4-羟基和4-氧代-2，2，6，6-四甲基哌啶-N-氧基(分别为羟基-TEMPO和氧代-TEMPO)相比，这些探针在小鼠肝匀浆中的EPR信号衰减明显受到抑制，而羟基-DICPO和氧代-DICPO与抗坏血酸的反应活性没有差异。在半胱氨酸存在下，羟基和氧代DICPO都能与羟基自由基反应，只有羟基DICPO与超氧阴离子自由基反应而失去EPR信号。这一特征类似于观察到的羟基和氧-TEMPO。这些结果表明，在氮氧基自旋探针中引入螺环己基可以有效地保护氮氧基不受酶还原的影响，而不会改变与氧自由基的反应特性。
To suppress enzymatic reduction of nitroxyl group of spin probes, this study designed two new nitroxyl probes, 4-hydroxy and 4-oxopiperidine-N-oxyls having 4'-hydroxyspirocyclohexyl groups at the 2- and 6-positions of the piperidine ring (hydroxy-DICPO and oxo-DICPO, respectively). The decay of the EPR signal of these probes in mouse liver homogenates was significantly suppressed compared with that of 4- hydroxy- and 4-oxo-2,2,6,6- tetramethylpiperidine-N-oxyl (hydroxy-TEMPO and oxo-TEMPO, respectively), although hydroxy-DICPO and oxo-DICPO showed no difference in the reactivities with ascorbic acid. While both hydroxy- and oxo-DICPO reacted with hydroxyl radicals, only hydoxy-DICPO lost its EPR signal by the reaction with superoxide anion radical in the presence of cysteine. This feature is similar to that observed for hydroxy- and oxo-TEMPO. These results suggest that the introduction of spirocyclohexyl groups to nitroxyl spin probes is effective for protecting the nitroxyl group against enzymatic reduction without changing the characteristics of the reaction with oxygen radicals.