The ortho effect makes Manganese(III) Meso-Tetrakis(N-Methylpyridinium-2-yl) porphyrin a powerful and potentially useful superoxide dismutase mimic

The ortho effect makes Manganese(III) Meso-Tetrakis(N-Methylpyridinium-2-yl) porphyrin a powerful and potentially useful superoxide dismutase mimic
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DOI:
10.1074/jbc.273.38.24521
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发表时间:
1998-09-18
影响因子:
4.8
通讯作者:
Fridovich, I
Fridovich, I
中科院分区:
生物学2区
文献类型:
--
作者:
Batinic-Haberle, I;Benov, L;Fridovich, I

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对锰(III)5,10,15,20-四(N-甲基吡啶基)卟啉MnTM-2-PyP 5+、MnTM-3-PyP 5+和MnTM-4-PyP 5+的邻位、Meta和帕拉异构体进行了体外和体内超氧化物歧化酶(SOD)活性分析。并分析了它们与DNA和RNA的相互作用对体内和体外SOD活性的影响。它们行为的差异是由于空间和静电因素的结合。体外催化活性与其氧化还原电位密切相关。半波电位(E-1/2)相对于正常氢电极为+0.220 mV、+0.052 mV和+0.060 V,而邻位、Meta和帕拉异构体的歧化速率(k(cat))分别为6.0 x 10(7)、4.1 x 10(6)和3.8 x 10(6)M-1 s(-1)。体外活性不是体内功效的充分预测因子。邻位和Meta异构体,虽然显着不同的体外SOD活性,有相当接近的体内SOD的功效,由于它们同样弱的相互作用与DNA。相反,由于与DNA的相互作用程度更高,帕拉异构体抑制SOD缺陷型大肠杆菌的生长。
The ortho, meta, and para isomers of manganese(III) 5,10,15,20-tetrakis(N-methylpyridyl)porphyrin MnTM-2-PyP5+, MnTM-3-PyP5+, and MnTM-4-PyP5+, respectively, were analyzed in terms of their superoxide dismutase (SOD) activity in vitro and in vivo. The impact of their interaction with DNA and RNA on the SOD activity in vivo and in vitro has also been analyzed. Differences in their behavior are due to the combined steric and electrostatic factors. In vitro catalytic activities are closely related to their redox potentials. The half-wave potentials (E-1/2) are +0.220 mV, +0.052 mV, and +0.060 V versus normal hydrogen electrode, whereas the rates of dismutation (k(cat)) are 6.0 x 10(7), 4.1 x 10(6), and 3.8 x 10(6) M-1 s(-1) for the ortho, meta, and para isomers, respectively.However, the in vitro activity is not a sufficient predictor of in vivo efficacy. The ortho and meta isomers, although of significantly different in vitro SOD activities, have fairly close in vivo SOD efficacy due to their similarly weak interactions with DNA. In contrast, due to a higher degree of interaction with DNA, the para isomer inhibited growth of SOD-deficient Escherichia coli.