电化学法研究苯磺酰类5-氟尿嘧啶衍生物与双链和G-四链DNA的相互作用

本文以自组装法制得的双链DNA（ds．DNA）和G-四链体DNA（G4-DNA）修饰的金电极为工作电极,以Fe（CN）63-／4-为电活性指示剂,采用循环伏安法和微分脉冲伏安法研究了非电活性苯磺酰类5-氟尿嘧啶衍生物与ds-DNA和G4．DNA的相互作用．实验结果表明：苯磺酰类5-氟尿嘧啶与ds-DNA或G4．DNA的结合常数与苯环上邻、对位取代基的得失电子能力密切相关,强吸电子基团取代有利于苯磺酰类5-氟尿嘧啶选择性结合G-四链体DNA．     

四种5-氟尿嘧啶二肽衍生物的合成、晶体结构和抗癌活性

合成了四种新的5-氟尿嘧啶(5-Fu)二肽衍生物, 它们的结构经过元素分析、IR、1H NMR和13C NMR的表征, 比旋光度[a]D的测定结果表明了它们之间的对映异构关系, 用X射线衍射法测定了其中一对对映异构的晶体结构3a (S)和3b (R), 生物活性测试的结果表明这四种化合物都具有一定的抑制活性, 并且R型产物比S型产物抑制率高. 研究了2a和3a与DNA在Au电极上相互作用的伏安行为, 比较了它们跟5-氟尿嘧啶与双链DNA发生相互作用的差别.     

钌配合物与G-四链体DNA的相互作用研究进展

人体端粒由富含鸟嘌呤(G)的DNA重复序列组成,该序列在一定条件下可以形成G-四链体DNA结构。小分子化合物诱导该结构的形成并使之稳定,可以抑制端粒酶活性而达到抗肿瘤的目的。因此,G-四链体DNA稳定剂的设计和筛选是近年来生物无机化学的重要前沿研究领域之一。在金属配合物中,钌配合物由于具有丰富的光化学、光物理特性以及生物活性,其作为G-四链体DNA稳定剂引起人们的高度关注。本文以近年一些代表性的研究工作为例,对钌配合物与G-四链体DNA相互作用方面的研究进展进行了综述。     

(R)-/(S)-2-(5-氟尿嘧啶-1-基-乙酰基)氨基-3-羟基丙酸甲酯和DNA相互作用的电化学研究

以自组装制得的DNA修饰电极为工作电极,采用循环伏安法以Fe(CN)63-/4-为电活性指示剂,研究了抗癌药物R型和S型的2-(5-氟尿嘧啶-1-基-乙酰基)氨基-3-羟基丙酸甲酯(简称为(R)-5FUSer和(S)-5FUSer)与DNA的相互作用.循环伏安测试结果表明:(1)体系的式电位随(R)-5FUSer和(S...     

类黄酮化合物对G-四链体及双链DNA选择性的电喷雾质谱研究

利用电喷雾质谱(ESI-MS)研究了4种常见的类黄酮化合物芦丁、 槲皮素、 葛根素和柚皮苷与2种不同形态结构的G-四链体DNA和3种双链DNA的非共价相互作用, 比较了这些小分子化合物与不同形态结构DNA结合的强弱及形成复合物的化学计量. 结果表明, 芦丁和槲皮素对G-四链体DNA具有一定的选择性, 同时它们对双链DNA的选择性也较高; 而葛根素和柚皮苷对G-四链体DNA仅显示了较低的选择性.     

DNA与5-氟尿嘧啶相互作用的电化学和谱学研究

以电位控制共价组装法制得的DNA修饰电极为工作电极, 采用循环伏安和方波脉冲伏安法, 以亚甲蓝(MB)为电活性指示剂, 研究了非电活性抗癌药物5-氟尿嘧啶(5-FU)与DNA的相互作用, 还结合紫外-可见光谱进一步研究了这种相互作用. 循环伏安测试结果表明: 5-FU与DNA在电极表面反应的过程为可逆电化学反应-化学反应偶合(EC)过程. 当扫描速度较低时, EC反应是扩散控制过程; DNA与电活性物质MB通过静电吸附相互结合, 抗癌药物5-FU与DNA通过插入作用相互结合. 本研究对于遗传工程中以DNA为靶标的药物设计有重要的意义.     

2-(5-氟尿嘧啶-1-基乙酰基)氨基乙酸的合成及表征

50多年来,5-氟尿嘧啶(5-FU)一直作为首选抗代谢药物用于临床治疗胃癌、结直肠癌、乳腺癌、肝癌等多种癌症[1-2].但由于其亲脂性较低以及生物利用度低,影响抗肿瘤疗效,且其治疗剂量与中毒剂量接近,从而给临床应用带来了一定的问题.     

炔基配体对2, 6-双(N-乙基苯并咪唑)吡啶炔基铂(Ⅱ)配合物与G-四链体作用及抗癌活性的影响

合成了三种2, 6-双(N-乙基苯并咪唑)吡啶炔基铂(Ⅱ)配合物(2-4),其中配合物2的炔基配体为抗癌药物埃罗替尼.利用紫外-可见(UV-Vis)吸收光谱,圆二色(CD)光谱,荧光共振能量转移(FRET)等方法研究了铂(Ⅱ)配合物与人体端粒(Hetelo)和c-myc原癌基因(c-myc)G-四链体的相互作用.实验结果表明,所合成的铂配合物与G-四链体具有较强的相互作用(K_a > 10⁶ L·mol^-1),在无碱金属离子存在条件下能诱导G-四链体的形成.含苯乙炔基团的配合物2、3能使c-myc G-四链体的熔解温度上升24 ℃以上,而含丙炔基团的铂配合物4仅使c-mycG-四链体的熔解温度升高9.0 ℃,表明炔基结构对铂(Ⅱ)配合物与G-四连体的作用有较大影响.配合物2对人肺癌细胞A549的细胞毒性明显高于埃罗替尼及其他两种配合物3、4.     

血红素/G-四链体DNA酶的活性增强研究及其在生物传感器中的应用进展

血红素/G-四链体DNA酶是一类具有类过氧化物酶活性的DNA分子,因其具有出色的活性、易修饰性和可编程性,被广泛应用于生物传感器等领域。 本文先是简要介绍了G-四链体的结构,再主要综述了增强血红素/G-四链体DNA酶活性的策略及基于血红素/G-四链体DNA酶的生物传感器在生物标志物、微生物与生物毒素以及金属离子检测中的应用,并展望了血红素/G-四链体DNA酶的未来发展趋势。     

基于G-四链体-氯化血红素DNA酶比色法测定银离子和汞离子传感器的构筑

利用G-四链体DNA(5′-CTGGGAGGGAGGGAGGGA-3′)与氯化血红素结合形成G-四链体-Hemin DNA酶,其能高效催化H_2O_2氧化反应底物由无色变为绿色,当溶液中有Ag~+或Hg~(2+)存在时会阻碍该DNA酶的形成,导致绿色溶液变浅。基于此,建立了比色法测定Ag~+和Hg~(2+)的传感器。在最佳实验条件下,溶液的吸光度与Ag~+和Hg~(2+)浓度分别在100.0～1 000.0 nmol/L和80.0～800.0 nmol/L范围内具有良好的线性关系,检出限(3δ/Slope)分别为55.9 nmol/L和64.3 nmol/L。该方法具有较好的选择性,采用该方法对实际样品进行测试,结果满意。     

Electrochemical investigation on the interaction of benzene sulfonyl 5-fluorouracil derivatives with double-stranded DNA and G-quadruplex DNA

The interaction of double-stranded(ds) and G-quadruplex(G4) DNA with sulfonyl 5-fluorouracil derivatives(5-fluoro-1-(arylsulfonyl) pyrimidine-2,4(1H,3H)-diones) was investigated in this research,in which Au electrodes modified with ds-DNA or G4-DNAs were used as a working electrode.The investigation showed that the binding affinity with G4-DNA was significantly increased when 5-fluorouracil(5-FU) was modified with arylsulfonyl groups.The presence of strong electron-withdrawing groups on benzene sulfonyl 5-FU greatly enhanced the binding selectivity(k G4-DNA /k ds-DNA).Such results provided new insights into the potential connections between the chemical structure of drug candidates and their anticancer activities.     

Interactions between meso-tetrakis(4-(N-methylpyridiumyl))porphyrin TMPyP4 and DNA G-quadruplex of telomeric repeated sequence TTAGGG

The binding properties between meso-tetrakis(4-(N-methylpyridiumyl))porphyrin (TMPyP4) and the parallel DNA G-quadruplex (G4) of telomeric repeated sequence 5′-TTAGGG-3′ have been characterized by means of circular dichroism,steady-state absorption,steady-state fluorescence and picosecond time-resolved fluorescence spectroscopies. The binding constant and the saturated binding number were determined as 1.29×106 (mol/L)-1 and 3,respectively,according to steady-state absorption spec-troscopy. Based on the findings by the use of time-resolved fluorescence spectroscopic technique,it is deduced that TMPyP4 binds to a DNA G-quadruplex with both the thread-intercalating and end-stacking modes and at the saturated binding state,one TMPyP4 molecule intercalates into the intervals of G-tetrads while the other two stack to the ends of the DNA G-quadruplex.     

基于聚硫堇、DNA/纳米银复合物共修饰癌胚抗原免疫传感器的研究

将硫堇聚合到玻碳电极(GCE)表面形成带正电的多孔聚硫堇(PTH)复合膜, 通过静电吸附固定DNA/纳米银复合物, 利用复合物中纳米银大的比表面积和强的吸附能力将癌胚抗体(anti-CEA)固定到电极表面, 从而制得高灵敏的电流型癌胚抗原(CEA)免疫传感器. 通过循环伏安法考察了电极表面的电化学行为, 并对免疫传感器的性能进行了详细研究. 在最优的实验条件下, 用示差脉冲伏安法(DPV)对癌胚抗原进行检测, 其线性范围为1.0～10.0 ng•mL^－1和10.0～80.0 ng•mL^－1, 线性相关系数分别为0.9983和0.9970, 检测限为0.24 ng•mL^－1, 并将该免疫传感器用于血清样品中CEA的检测.     

5-氟尿嘧啶-1-乙酸合铜(Ⅱ)的合成及其与DNA的作用

The 5-fluorouracil-1-acetic acid (5FuAA) and its Cu(Ⅱ) complex (5FuAACu) were synthesized and the date for the crystal complex was obtained. The interaction of 5-fluorouracil-1-acetic acid (5FuAA) and its Cu(Ⅱ) complex (5FuAACu) with DNA was also investigated by using spectral, viscometric, electrochemical and agarose gel electrophoresis methods. The results of interaction with DNA suggest that both 5FuAA and 5FuAACu can bind to DNA in a static electricity attraction mode. But the attraction of 5FuAACu is greater than that of 5FuAA.     

Interactions between meso-tetrakis(4-(<Emphasis Type="Italic">N</Emphasis>-methylpyridiumyl))porphyrin TMPyP4 and DNA G-quadruplex of telomeric repeated sequence TTAGGG

The binding properties between meso-tetrakis(4-(N-methylpyridiumyl))porphyrin (TMPyP4) and the parallel DNA G-quadruplex (G4) of telomeric repeated sequence 5′-TTAGGG-3′ have been characterized by means of circular dichroism, steady-state absorption, steady-state fluorescence and picosecond time-resolved fluorescence spectroscopies. The binding constant and the saturated binding number were determined as 1.29×10⁶ (mol/L)⁻¹ and 3, respectively, according to steady-state absorption spectroscopy. Based on the findings by the use of time-resolved fluorescence spectroscopic technique, it is deduced that TMPyP4 binds to a DNA G-quadruplex with both the thread-intercalating and end-stacking modes and at the saturated binding state, one TMPyP4 molecule intercalates into the intervals of G-tetrads while the other two stack to the ends of the DNA G-quadruplex. Supported by the National Natural Science Foundation of China (Grant Nos. 20442004, 10576002 and 20703067)     

Lable‐Free Electrochemical DNA Sensor Based on Gold Nanoparticles/Poly(neutral red) Modified Electrode

We present a new strategy for the label‐free electrochemical detection of DNA hybridization based on gold nanoparticles (AuNPs)/poly(neutral red) (PNR) modified electrode. Probe oligonucledotides with thiol groups at the 5‐end were covalently linked onto the surface of AuNPs/PNR modified electrode via S‐Au binding. The hybridization event was monitored by using differential pulse voltammetry (DPV) upon hybridization generates electrochemical changes at the PNR‐solution interface. A significant decrease in the peak current was observed upon hybridization of probe with complementary target ssDNA, whereas no obvious change was observed with noncomplementary target ssDNA. And the DNA sensor also showed a high selectivity for detecting one‐mismatched and three‐mismatched target ssDNA and a high sensitivity for detecting complementary target ssDNA, the detection limit is 4.2×10^?12 M for complementary target ssDNA. In addition, the DNA biosensor showed an excellent reproducibility and stability under the DNA‐hybridization conditions.     

Crystal Structure and Biological Activities of N-(5-(4-Chloro-2-(trifluoromethyl)phenyl)furan-2- carbonyl)-N'-(4,6-dimethylpyrimidin-2-yl)thiourea

The new title compound N-(5-(4-chloro-2-(trifluoromethyl)phenyl)furan-2-carbon-yl)- N?-(4,6-dimethylpyrimidin-2-yl)thiourea (C19H14ClF3N4O2S) has been synthesized, and its crystal structure and biological behaviors were studied. The title compound crystallizes in the monoclinic system, space group P21/c with a = 7.932(5), b = 33.46(2), c = 7.556(5) , β = 98.058(9)°, V = 1986(2) 3, Mr = 454.85, Z = 4, Dc = 1.521 g/cm3, μ = 0.349 mm–1 and F(000) = 928. The structure was solved by direct methods and refined to R = 0.0724 and wR = 0.1429 for 3494 observed reflections (I > 2σ(I)). Intermolecular hydrogen bonds along the b axis together with the continuous π-π interactions construct the three-dimensional architecture of the title compound. The preliminary biological tests show definite herbicidal activity for the title compound.     

N-(2-(5-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-1,3,4-噁二唑-2-基)-4-氯-6-甲基苯基)酰胺类新化合物的合成及生物活性

以N-吡啶基吡唑甲酸和2-氨基-3-甲基苯甲酸为起始原料,经由亲核加成、环化和酰化等多步反应合成了一系列结构新颖的N-(2-(5-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-1,3,4-噁二唑-2-基)-4-氯-6-甲基苯基)酰胺类化合物.测试了所合成化合物的杀虫及抑菌活性,结果表明,新化合物大多化合物在200 mg·L^-1浓度下对东方粘虫(Mythimna separataWalker)具有一定的杀虫活性,尤其是N-(2-(5-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-1,3,4-噁二唑-2-基)-4-氯-6-甲基苯基)乙酰胺(8a)和N-(2-(5-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-1,3,4-噁二唑-2-基)-4-氯-6-甲基苯基)-3-氯-2,2-二甲基丙酰胺(8e)致死率可达70%;部分化合物在50 mg·L^-1浓度下对油菜菌核病菌的抑菌活性相对较好(54.5%~63.6%),优于triadimefon和chlorantraniliprole;部分化合物如N-(2-(5-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-1,3,4-噁二唑-2-基)-4-氯-6-甲基苯基)-3,3-二甲基丁酰胺80和N-(2-(5-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-1,3,4-噁二唑-2-基)-4-氯-6-甲基苯基)-4-氟苯甲酰胺(8h)对苹果轮纹病菌具有中等抑菌活性.值得注意的是,化合物8e的杀粘虫活性和对油菜菌核病菌的抑菌活性都较为突出,可用作新农药创制研究的新型参考结构.