Blaskó A, Browne K A, Bruice T C
Department of Chemistry, University of California, Santa Barbara 93106, USA.
Bioorg Med Chem. 1995 Jun;3(6):631-46. doi: 10.1016/0968-0896(95)00051-h.
The solution structure of a 1:1 complex of zinc tren-microgonotropen-b [6b:Zn(II)] with d(CGCAAATTTGCG)2 has been determined by 2D nuclear Overhauser effect 1H NMR spectroscopy and restrained molecular modeling. The exchangeable and nonexchangeable proton resonances of d(CGCA3T3GCG)2:6b:Zn(II) indicate that the Zn(II) is interacting in the A+T-rich region of the dsDNA and the tren region of 6b, while 31P NMR shows interaction of the Zn(II) with the phosphate backbone. Proton chemical shift differences between d(CGCA3T3GCG)2:6b:Zn(II) and d(CGCA3T3GCG)2:6b are in agreement with the polyamino substituent of 6b [-(CH2)4N(CH2CH2)N-(CH2CH2NH2)2] forming a four-coordinated Zn(II) complex similar to that found in the X-ray structure of 'tren-chloride':Zn(II). The P9 and P10 phosphate oxygens that are held by hydrogen bonding to the tren substituent of 6b in the DNA:6b complex become ligands to the tren-complexed Zn(II) in DNA:6b:Zn(II). To do so there is a 2 A decrease in the adjacent phosphate-to-phosphate distance at the Zn(II) binding site. This motion brings about an increased bend of 14.6 degrees in the helical axis of d(CGCA3T3GCG)2:6b:Zn(II) compared to that found in d(CGCA3T3GCG)2:6b. Single stranded cleavage of linear DNA fragments was not observed in the presence of 6b and Fe(II), Co(II), Ni(II), Cu(II), Zn(II), La(III) or Ce(III); this is likely due to the metal ion being sequestered as in the structure of d(CGCA3T3GCG)2:6b:Zn(II) complex. Supercoiled DNA was susceptible to cleavage by 6b:Cu(II) in the presence of O2 and a reducing agent.
通过二维核Overhauser效应1H NMR光谱和受限分子建模确定了锌tren-微促性腺激素-b [6b:Zn(II)]与d(CGCAAATTTGCG)2的1:1复合物的溶液结构。d(CGCA3T3GCG)2:6b:Zn(II)的可交换和不可交换质子共振表明，Zn(II)在dsDNA的富含A+T区域和6b的tren区域相互作用，而31P NMR显示Zn(II)与磷酸骨架相互作用。d(CGCA3T3GCG)2:6b:Zn(II)和d(CGCA3T3GCG)2:6b之间的质子化学位移差异与6b的多氨基取代基[-(CH2)4N(CH2CH2)N-(CH2CH2NH2)2]形成类似于在“tren-氯化物”:Zn(II)的X射线结构中发现的四配位Zn(II)复合物一致。在DNA:6b复合物中通过氢键与6b的tren取代基结合的P9和P10磷酸氧在DNA:6b:Zn(II)中成为tren-络合Zn(II)的配体。为此，Zn(II)结合位点处相邻磷酸酯与磷酸酯之间的距离减少了2 Å。与d(CGCA3T3GCG)2:6b相比此运动使d(CGCA3T3GCG)2:6b:Zn(II)的螺旋轴增加了14.6度的弯曲。在6b和Fe(II)、Co(II)、Ni(II)、Cu(II)、Zn(II)、La(III)或Ce(III)存在下未观察到线性DNA片段的单链切割；这可能是由于金属离子如在d(CGCA3T3GCG)2:6b:Zn(II)复合物结构中那样被螯合。超螺旋DNA在O2和还原剂存在下易被6b:Cu(II)切割。
