三核铜配合物[Cu_3L_2](ClO_4)_2(H_2L=1,3-双（2-羟基-1-苯基-亚甲基）-丙烷)的合成与对pBR322DNA的切断作用

利用席夫碱配体[H_2L = 1，3-双（2-羟基-1-苯基-亚甲基）-丙烷]与铜盐作 用，得到了配合物[Cu_3L_2](ClO_4)_2，并用X射线单晶衍射测定了其晶体结构。 研究了该三核铜配合物与质粒pBR322 DNA之间的相互作用，琼脂糖凝胶电泳实验结 果表明该配合物能够将pBR322 DNA从超螺旋构型切割成开环型和线型。同时，紫外 光谱实验可以推测，配合物在对pBR322 DNA进行切断时，它们之间在一种插入作用 。     

Analysis of Diazofluorene DNA Binding and Damaging Activity: DNA Cleavage by a Synthetic Monomeric Diazofluorene

The lomaiviticins and kinamycins are complex DNA damaging natural products that contain a diazofluorene functional group. Herein, we elucidate the influence of skeleton structure, ring and chain isomerization, D‐ring oxidation state, and naphthoquinone substitution on DNA binding and damaging activity. We show that the electrophilicity of the diazofluorene appears to be a significant determinant of DNA damaging activity. These studies identify the monomeric diazofluorene 11 as a potent DNA cleavage agent in tissue culture. The simpler structure of 11 relative to the natural products establishes it as a useful lead for translational studies.     

DNA Cleavage of the Copper（II） Complexes with a Polyamine Ditopic Ligand

The investigations on simple and efficient reagents, which can cleave nucleic acids undermild conditions have been attracted considerable attentions1,2. Generally, in order toeliminate the possibility of significant cytotoxic side effect of reactive oxygen species,pathways that result in DNA cleavage by hydrolysis mechanisms are preferable3,4. Wehave reported two novel metal complexes magnesium (II)-diethylenetriamine (dien) andcopper (II)-L-histidine systems that both can effectively promo…     

金属有机配合物对DNA的断链作用

过渡金属配合物催化DNA、RNA的断链反应研究是近年来最为活跃的前沿研究领域之一,因某些金属配合物具有核酸酶特异性催化DNA、RNA断链的功能,因而该研究对新型抗肿瘤、抗艾滋病化学药物的定向设计及其基因治疗和分子生物学研究中DNA、RNA的高度专一性定点断裂、染色体图谱分析及DNA定位诱变、基因工程中足迹技术(footprinting)以及DNA构象识别等方面均具有重要意义和应用前景,文献已报道了一些具有断裂DNA、RNA功能的金属配合物,但其中很少有含金属-碳σ键的金属有机化合物,本文首次报道了二茂铁鎓离子三氯乙酸盐和二氯二茂钛对DNA的断链作用。     

全反式维甲酸合钇(Ⅲ)配合物对DNA的切割和键合作用(英)

以紫外光谱、荧光光谱、粘度法和凝胶电泳方法研究了全反式维甲酸合钇(Ⅲ)配合物与DNA的作用。结果表明，该配合物能在生理条件下比配体和金属离子更有效地切割质粒DNA，体系离子强度和pH值的变化对配合物的切割活性有较大影响，自由基捕捉剂的加入不影响配合物的切割活性。该配合物对DNA的切割可能通过水解机理进行。该配合物可使DNA的粘度增加，使EB-DNA体系的荧光强度和DNA溶液的紫外吸收强度降低。据此推断，该配合物主要以嵌入方式与DNA作用。     

DNA Binding and Cleavage Activity of cis‐Cobalt Aromatic Oxime Complexes and Its Pyridine/imidazole Adducts

cis‐Cobalt complexes with salicycaldoxime(SAO), (Z)‐1‐(2‐hydroxyphenyl)ethanonoxime (HEO), (Z)‐1‐(2,5‐dihydroxyphenyl)ethanonoxime (DEO), (Z)‐1‐(2,5‐dihydroxyphenyl)(phenyl)methanonoxime (DPO) and their adducts with pyridine (Py) and imidazole (Im) were synthesized and characterized by elemental analysis, magnetic susceptibility, UV‐Vis and IR spectra. The electrochemical studies were carried by cyclic voltammeter, the peak potential separation and formal potential of complexes were independent of sweep rate or scan rate (ν) indicating a quasi reversible one‐electron redox process. Absorption studies and thermal denature studies revealed that each of these octahedral complexes is an avid binder of calf thymus DNA. The apparent binding constants for mixed ligand complexes are in order of ～10³‐10³ M^?1. Based on the data obtained in the DNA binding studies a partial intercalative mode of binding is suggested for these complexes. The nucleolytic cleavage activity of parent complexes and their pyridine adduct were carried out on double stranded pBR322 circular plasmid DNA by using a gel electrophoresis experiment in the presence and absence of oxidant (H₂O₂). All the metal complexes show enhanced cleavage activity in presence of oxidant. The hydrolytic cleavage of DNA of Co(DEO)₂ and Co(DPO)₂ is evidenced from the control experiments showing discernable cleavage inhibition in the presence of the hydroxyl radical inhibitor DMSO and EDTA.     

DNA Cleavage Promoted by Cu^2＋ Complex of N,N＇-Bis（2-aminoethyl）-2,6-pyridinedicarboxamide

The interaction of Cu^2＋ complex of N,N＇-bis（2-aminoethyl）-2,6-pyridinedicarboxamide （BAP） with DNA was studied by agarose gel electrophoresis analysis. The results indicate that the BAP-Cu^2＋ complex can promote the cleavage of phosphodiester bond of supercoiled DNA at physiological condition, which is 3.2 × 10^6 times higher than DNA natural degradation. A hydrolytic cleaving mechanism through the cooperation of copper ions and functional amino groups was proposed.     

缬氨酸Schiff碱金属铜配合物对质粒DNA的切割作用

缬氨酸Schiff碱金属铜配合物(PBP-L-Val-Cu)是新合成的一类非酶类切割工具, 合成了4种类型样品分别为L-CH3 Cu, D-CH3 Cu, L-Ph Cu和D-Ph Cu. 以质粒DNA(pUC18)为材料,分别对这4种类型化合物进行核酸切割效率的研究, 得出适合的反应体系后, 通过琼脂糖凝胶电泳对反应不同时间后核酸切割产物进行检测, 最终分别得到每种化合物将超螺旋型DNA切割成为开环型DNA和直线型DNA的切割效率, 经比较得出L-CH3 Cu型的切割效率是最快的. 将直线型DNA切割产物用琼脂糖凝胶回收试剂盒进行回收, 得到的直线型切割产物可以在T4连接酶的作用下重新连接起来. 利用酶切法对切口进行检测, 结果表明, 切割作用是具有特异性的. 另外, 该化合物对质粒pNQ216也具有切割活性.     

结合丝组二肽的树状多肽对λDNA的切割

以Fmoc手工固相合成法合成了以多聚赖氨酸为骨架, 表面结合丝组二肽的四分支和二分支树状多肽, 以高效液相色谱提纯, 电喷雾电离质谱表征, 并通过凝胶电泳法研究了其对λDNA的切割活性.     

Photoinduced DNA Cleavage and Photocytotoxic of Phenanthroline-Based Ligand Ruthenium Compounds

The photophysical and biological properties of two new phenanthroline-based ligand ruthenium complexes were investigated in detail. Their DNA interaction modes were determined to be the intercalation mode using spectra titration and viscosity measurements. Under irradiation, obvious photo-reduced DNA cleavages were observed in the two complexes via singlet oxygen generation. Furthermore, complex 2 showed higher DNA affinity, photocleavage activity, and singlet oxygen quantum yields than complex 1. The two complexes showed no toxicity towards tumor cells (HeLa, A549, and A375) in the dark. However, obvious photocytotoxicities were observed in the two complexes. Complex 2 exhibited large PIs (phototherapeutic indices) (ca. 400) towards HeLa cells. The study suggests that these complexes may act as DNA intercalators, DNA photocleavers, and photocytotoxic agents.     

二价金属离子激活铜超氧化物歧化酶断裂DNA的活性

以铜超氧化物歧化酶(CunSOD, n＝1—4)作为野生型CuZnSOD突变体的一种模型, 研究了其在二价金属离子(Mg2+, Mn2+)存在下由非氧化途径断裂DNA的活性, 并与CuZnSOD和脱辅基SOD(apoSOD)进行了比较. 结果表明, 在Mg2+或Mn2+存在下, CunSOD断裂DNA的活性高于CuZnSOD和apoSOD, 并且DNA的断裂活性受二价金属离子浓度、pH及酶浓度等因素影响. 相对活性及动力学参数的测定结果表明, CunSOD断裂DNA的相对能力按Cu1SOD2SOD≈Cu4SOD3SOD的顺序变化.     

Synthesis and Cleavage Activity of Artifical Minic Polypeptides

Natural product distamycin and netropsin are polyamide containing three N-methyl- pyrrole (Py) moieties. They have ability to binding to the minor groove of A·T-rich sequences of double–helical DNA. Thus, much attention has been attracted to the synthes…     

Synthesis and DNA Cleavage Studies of 2,6-Dimethoxyhydroquinone-3-Mercaptoacetic Acid Conjugates

In previous paper and work, we reported the synthesis and cytotoxicity studies of a novel series of short chain peptide conjugates of the cytotoxic agent 2, 6-dimethoxyhydro -quinone-3-mercaptoacetic acid1 (DMQ-MA). The DMQ-MA is a derivative of 2,6-dimethoxybenzoquinone, which is a natural product of fermented wheat germ and found to have a wide spectrum of cytotoxicity against various tumor cell lines under the synergistic activation of L-ascorbic acid (AH2)2,3. Compared with DMQ, DMQ…     

Synthesis and DNA Cleavage Properties of Triazacrown Derivatives

New metal‐free DNA cleaving reagent 1 , 1,4,7‐triazacrown (TACN) both with aminoethyl, hydroxyethyl side arms and a planar anthraquinone linked by an alkyl (1,6‐hexamethylene) spacer has been synthesized and characterized by NMR and MS spectrometry. For comparison, the corresponding aminoethyl, hydroxyethyl triazacrown derivative 2 without the anthraquinone has also been synthesized. DNA‐binding properties via fluorescence and CD spectroscopy indicate that the binding affinity of 1 with DNA is much stronger than that of 2 . Agarose gel electrophoresis was used to assess plasmid pUC19 DNA cleavage. Kinetic data of DNA cleavage promoted by 1 , 2 and parent triazacrown (TACN) 3 under physiological condition give the 15‐fold and 234‐fold rate acceleration of compound 1 over 2 and parent triazacrown 3 . Radical scavenger inhibition study suggests that DNA cleavage promoted by 1 may be a non‐oxidative pathway through the transphosphorylation and then hydrolysis. The dramatic rate acceleration is due not only to the anthraquinone moiety of compound 1 intercalating into DNA base pairs via stacking interaction, but also the cooperative catalysis of the nucleophilic hydroxyl and the electrophilic ammonium group for the cleavage of phosphodiester of DNA.     

利用荧光标记引物和DNA自动测序仪确定DNA的断裂位点

建立了利用荧光标记引物和DNA自动测序仪进行DNA断裂位点分析的新方法, 该方法简便易行、灵敏度高、重复性好、数据分析客观性强、结果可靠, 适用于各种因素造成的DNA断裂位点的分析.     

Interaction between Bifunctional Dioxo Macrocyclic Polyamine Co(II) Complex and DNA in Metallomicellar System

Artificial enzymes are non-protein molecules that are more simple than natural enzymes, but they also possess high efficiency and specificity. In recent years, the study of enzyme models is one of the most active fields1-2, especially chemical nuclease. Micelles, dynamic colloidal aggregates formed by amphipathic surfactant molecules, can mimic the hydrophobic structure of active site of enzymes because they offer a hydrophobic microenviornment which is similar to the important part located …     

Efficient Cleavage of DNA by the Novel Copper (II) Complex Derived From 2,2'-Pyridil Ligand

Due to the importance of oxidative degradation of nucleic acids in mutagenesis, carcinogenesis, and aging, a large number of chemical and biological investigations have been recently published1. Artificial metallonucleases have been proven to be efficient tools for the footprinting and sequence-specific targeting of nucleic acids1,2. They usually require high concentrations of the complex and of an external reducing agent (such as dithiothreitol, DTT) to form a reactive species in situ, the f…     

丝组二肽对DNA切割作用的QM-MM研究

运用QM-MM方法对丝组二肽切割DNA作用的机理进行了研究．通过计算得到了丝组二肽与DNA形成多氢键作用的有效分子识别模型及相关分子结构参数,从理论上解释了丝组二肽与DNA通过形成五配位磷中间体而使磷酸二酯键发生水解,从而使得DNA被切断的作用机理。