Orientation of iron bleomycin and porphyrin complexes on DNA fibers.
Orientation of iron bleomycin and porphyrin complexes on DNA fibers.
复制标题
铁博来霉素和卟啉复合物在 DNA 纤维上的取向。
DOI：
10.1021/ic991365r
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发表时间：
2000
影响因子：
4.6
通讯作者：
D. Petering
中科院分区：
文献类型：
--
作者：
M. Chikira;T. Iiyama;K. Sakamoto;W. Antholine;D. Petering
博来霉素（Blm）是一种抗肿瘤剂，其需要铁和氧来切割DNA链。在这项研究中，铁博莱霉素，铁（III）Blm，或一氧化氮加合物的亚铁博莱霉素，ON-铁（II）Blm，绑定到一维定向的DNA纤维。还原亚硝基化的Fe（III）络合物发生在原位的B型DNA纤维。电子顺磁共振（EPR）谱作为磁场B和纤维轴Zf之间的角度φ的函数。为了比较，获得了ON-Fe（II）TMPyP和ON-Fe（II）TMPyP-Im在定向DNA纤维上的EPR谱，其中TMPyP是5，10，15，20-四（1-甲基-4-吡啶基）卟啉，Im是咪唑。EPR谱表明低自旋Fe（III）Blm和ON-Fe（II）Blm以两种略微不同的结合取向以1：0.2的比例与B型DNA结合。对于A型DNA，一部分结合的Fe（III）Blm是高自旋的。具体地，纤维轴Zf与垂直于或几乎垂直于铁络合物的赤道面的g轴gz之间的角度β被估计为对于ON-Fe（II）Blm分别为20度和25度，并且对于Fe（III）Blm分别为30度和25度。确定gx和戈伊轴取向的角度γ估计为对于两种ON-Fe（II）Blm物质为90度，对于两种Fe（III）Blm物质为10度。当温度从123 K升高到室温时，ON-Fe（II）Blm的NO刚性地保持在原位，但ON-Fe（II）TMPyP或ON-Fe（II）TMPyP-Im的NO没有刚性地保持在原位。假设NO通过氢键在结构上取向，就像过氧化物保持在HO 2（-）-Co（III）Blm中一样（Wu等人，J. Am. 1996，118，1281-1294）。的EPR参数是一致的六位配合物的ON-Fe（II）Blm，虽然从反式氮的superhyperfine结构没有检测到。当ON-Fe（II）Blm与DNA纤维结合时，g值各向异性的增加可能是由NO与DNA的相互作用引起的d π和2 p π * 轨道的重叠增加和/或由于嘧啶-鸟嘌呤相互作用引起的d轨道的扰动引起的。它的结论是，结合到定向DNA的ON-Fe（II）Blm和Fe（III）Blm的EPR参数支持的假设，FeBlm物种结合到DNA的加合物结构类似于由相关的CoBlm物种和DNA形成的。
Bleomycin (Blm) is an antitumor agent that requires iron and oxygen for strand cleavage of DNA. In this study, ferric bleomycin, Fe(III)Blm, or the nitric oxide adduct of ferrous bleomycin, ON-Fe(II)Blm, were bound to one-dimensionally oriented DNA fibers. Reductive nitrosylation of Fe(III) complexes took place in situ on B-form DNA fibers. Electron paramagnetic resonance (EPR) spectra were obtained as a function of the angle phi between the magnetic field B and the fiber axis Zf. For comparison, EPR spectra were acquired for ON-Fe(II)TMpyP and ON-Fe(II)TMpyP-Im on oriented DNA fibers, where TMpyP is 5,10,15,20-tetrakis(1-methyl-4-pyridino)porphyrin and Im is imidazole. EPR spectra showed both low-spin Fe(III)Blm and ON-Fe(II)Blm bound to B-form DNA in two slightly different binding orientations in the ratio of 1:0.2. With A-form DNA, a fraction of bound Fe(III)Blm was high spin. Specifically, the angle beta between the fiber axis Zf and the g axis, gz, perpendicular to or nearly perpendicular to the equatorial plane of the iron complex was estimated as 20 degrees and 25 degrees for ON-Fe(II)Blm and 30 degrees and 25 degrees for Fe(III)Blm, respectively. The angle gamma that determines the orientation of gx and gy axes was estimated as 90 degrees for the two ON-Fe(II)Blm species and 10 degrees for the two Fe(III)Blm species, respectively. The NO was held rigidly in place as the temperature increased from 123 K to room temperature for ON-Fe(II)Blm but not for ON-Fe(II)TMpyP or ON-Fe(II)TMpyP-Im. It is hypothesized that the NO is structurally oriented by hydrogen bonding like the peroxide is held in HO2(-)-Co(III)Blm (Wu et al. J. Am. Chem. Soc. 1996, 118, 1281-1294). The EPR parameters are consistent with a six-coordinate complex for ON-Fe(II)Blm, although the superhyperfine structure from the trans nitrogen was not detected. The increase in g value anisotropy upon binding ON-Fe(II)Blm to DNA fiber may be caused by an increase in the overlap of d pi and 2p pi* orbitals induced by an interaction of NO with DNA and/or by a perturbation of d orbitals due to the pyrimidine-guanine interaction. It is concluded that the EPR parameters of ON-Fe(II)Blm and Fe(III)Blm bound to oriented DNA support the hypothesis that FeBlm species bind to DNA with adduct structures similar to those formed by related CoBlm species and DNA.