咪唑-金属配合物的合成、性质及其与DNA的作用机理

Three hexakis（imidazole）metallo complexes of Co, Cd and Ni were synthesized and spectroscopically characterized. The crystal and molecular structures have been determined by X-ray crystallography analysis. The metal ions have an octahedral geometry with the MN6 chromophore. The electrochemical experimental results indicate that both [Co（Im）6]C12·2HCl·2H2O （1） and [Ni（Im）6]C12·4H2O （3） [Im=imidazole] could interact with DNA mainly by intercalation.     

喜树碱类抗肿瘤药物作用模式的柔性分子对接研究

研究采用柔性分子对接技术，将15个喜树碱类化合物对接到拓扑异构酶I (Topo I)-DNA切割复合物中，从原子水平和分子力场角度阐明了喜树碱类抗肿瘤药 物与DNA，Topo I的相互作用机制。研究发现，喜树碱分子插入Topp I-DNA复合物 的切割位点，并与Asn722，Asp533，Lys532和Lys720形成氢键作用网络。定量构效 关系研究进一步表明喜树碱分子可以与Topo I-DNA切割复合物形成电荷迁移作用。 该对接模型系统解释了喜树碱类化合物的构效关系、定点突变等诸多实验事实，为 下一步设计、合成新型高效的喜树碱类衍生物打下了坚实基础。     

Interaction of zinc finger ZNF191(243—368) and its I323 W and R327W mutants with oligonucleotides by florescence spectrum

Two mutants of the zinc finger protein, ZNF191 (243–368) I323W and R327W, are successfully obtained by site-directed mutagenesis. The fluorescence spectrum is used to study the interaction between these two mutants and the oligonucleotides. The influence of the mutation on the interaction has been studied using ethidium bromide (EB) as the fluorescence probe. The binding constants of the I323W-DNA and R327W-DNA have been calculated and the possible binding models have been discussed.     

Λ-、△-[Rh（bpy）2chrysi]^3＋对含C：T错配的DNA序列识别作用的分子模拟研究

通过分子模拟方法研究了手性金属配合物[Rh（bpy）2Chrysi]^3＋（bpy=2，2’-bipyridineChrysi=5，6-chrysenequinonediimine）对包含C：T错配碱基对的B-DNA序列的识别作用．结合类似的针对含G：A错配的和正常的B-DNA序列的识别作用研究，发现配合物I-Rh（bpy）zChrysi]^3＋可以对错配B-DNA序列进行序列特异性的识别．能量对比计算结果表明，该经典插入识别作用倾向于在错配碱基对附近进行，其中△-[Rh（bpy）2chrysi]^3＋比其手性异构体更占优势．这同Barton教授工作组的实验结果是一致的．另外插入作用倾向于在错配序列中的正常双碱基对C3A4／G3T4（错配碱基对附近）中从小沟进行．与该配合物对含G：A错配的和正常的B-DNA序列的识别作用不同的是，对包含C：T错配碱基对的B-DNA序列的识别作用倾向于从小沟进行．这一点可能源于C：T碱基对结构的不同．     

Voltammetric study of the interaction of lomefloxacin (LMF)–Mg(II) complex with DNA and its analytical application

The voltammetric behavior of the LMF-Mg(II) complex with DNA at a mercury electrode is reported for the first time. In NH₃–NH₄Cl buffer (pH=9.10), the adsorption phenomena of the LMF–Mg(II) complex were observed by linear sweep voltammetry. The mechanism of the electrode reaction was found to be a reduction of LMF in the complex, and the composition of the LMF–Mg(II) complex is 2:1. In the presence of calf thymus DNA (ctDNA), the peak current of LMF–Mg(II) complex decreased considerably, and a new well-defined adsorptive reduction peak appeared at −1.63 V (vs. SCE). The electrochemical kinetic parameters and the binding number of LMF–Mg(II) with ctDNA were also obtained. Moreover, the new peak currents of LMF–Mg(II)–DNA system increased linearly correlated to the concentration of DNA in the 4.00×10⁻⁷–2.60×10⁻⁶ g ml⁻¹ range when the concentrations of LMF–Mg(II) complex was fixed at 5.00×10⁻⁶ mol l⁻¹, with the detection limits of 2.33×10⁻⁷ g ml⁻¹. An electrostatic interaction was suggested by electrochemical method.     

FABRICATION OF SELF-ASSEMBLY DNA-C_(60) MULTILAYER FILMS

Electrostatic layer-by-layer self-assembly multilayer films were successfully fabricated from C_(60)-ethylenediamineadduct (C_(60)-EDA) and DNA. Under visible light irradiation, DNA is ready to be cleaved and the films are destroyed.     

On-channel base stacking in microchip capillary gel electrophoresis for high-sensitivity DNA fragment analysis

We evaluated a novel strategy for high-sensitivity DNA fragment analysis in a conventional glass double-T microfluidic chip. The microchip allows for a DNA on-channel concentration based on base stacking (BS) with a microchip capillary gel electrophoretic (MCGE) separation step in a poly(vinylpyrrolidone) (PVP) sieving matrix. Depending if low conductivity caused a neutralization reaction between the hydroxide ions and the run buffer component Tris+, the stacking of DNA fragments were processed in the microchip. Compared to a conventional MCGE separation with a normal electrokinetic injection, the peak heights of 50-2650-base pair (bp) DNA fragments on the MCGE-BS separation were increased 3.9-8.0-fold. When we applied the MCGE-BS method to the analysis of a clinical sample of bovine theileria after PCR reaction, the peak height intensity of the amplified 816-bp DNA fragment from the 18S rRNA of T. buffeli was enhanced 7.0-fold compared to that of the normal injection method.     

DNAzyme amplification of molecular beacon signal

This paper reports an improved catalytic molecular beacon. Addition of the target oligonucleotide activates a DNA enzyme (DNAzyme), which, in turn, activates multiple copies of molecular beacons (MB) and gives rise to a strong fluorescence signal. In a previous design, the activated DNAzyme could oligomerize, especially dimerize, and result in inactivation of the DNAzyme. The current design avoids this problem, upon activated by the target DNA, the DNAzyme will stay constantly active. With the improved method, a detection of 10 pM DNA has been demonstrated, which is 1000 times more sensitive than the method previously reported.     

Investigation of the Interactions of β‐Peptides with DNA Duplexes by Circular Dichroism Spectroscopy

The interaction of β‐peptides with the DNA duplexes of dA₂₀dT₂₀ and a GCN4‐binding CRE sequence was examined. To gauge the factors that govern these interactions, two β‐pentadecapeptides, 1 and 2 , a β‐dodecapeptide, 3 , three β‐decapeptides, 4 – 6 , three β‐heptapeptides, 7 – 9 , and β‐octaarginine 10 were designed and synthesized. The β‐peptides were conceived to adopt a β‐peptide 3₁₄ helix, in which the side chains at position i and i + 3 are aligned vertically along one side of the helix. The side chains of Lys, Asn, and Arg were positioned such that potential H‐bonding sites were created for a helical conformation to interact with the base pairs of DNA. CD Analysis showed that β‐peptides 1, 2 , and 10 interacted with dA₂₀dT₂₀. In addition, β‐peptides 1 and 2 showed significant interaction with a DNA‐duplex 20mer containing the ATF/CREB recognition sequence for the regulatory protein GCN4. It is impossible, at this stage of the investigation, to make a safe proposal about the actual nature of the interaction of the structures(s) of the complexes, the formation of which is suggested by the CD spectra reported herein.