靶向作用G-四链体DNA的金属配合物的研究进展

富含鸟嘌呤（G）碱基DNA能够通过Hoogsteen氢键形成四螺旋结构,该结构被称为G-四链体。诱导端粒DNA形成G-四链体并稳定该结构能起到抑制端粒酶活性,从而达到促进肿瘤细胞凋亡的作用。近年来,G-四链体DNA已成为设计抗肿瘤药物的重要靶点,文章综述铂（Ⅱ）配合物、钌（Ⅱ）配合物、镍（Ⅱ）配合物、铜（Ⅱ）配合物、锌（Ⅱ）配合物及其他金属配合物靶向作用G-四链体DNA的研究进展。     

铁-氟尿嘧啶配合物对人胃癌细胞凋亡的影响

目的研究铁-氟尿嘧啶配合物对人胃癌细胞SGC-7901的细胞毒活性及对细胞凋亡的影响。方法采用MTT法检测配合物及其配体对SGC-7901的增殖抑制作用,流式细胞术检测配合物及其配体对SGC-7901细胞凋亡的影响,实时荧光定量PCR法检测配合物及其配体对凋亡相关因子Caspase-8基因表达的影响。结果配合物能明显抑制SGC-7901细胞的增殖,IC_(50)为35μM,抑制作用强于其配体氟尿嘧啶和邻菲罗啉。配合物在10、20、40μM浓度时能明显促进SGC-7901细胞凋亡,作用强于其配体5-Fu和Phen;配合物能使凋亡相关因子Caspase-8在mRNA水平的表达上调。结论铁-氟尿嘧啶配合物的合成使其配体间形成了协同作用,具有良好的体外抗肿瘤活性。铁-氟尿嘧啶配合物诱导细胞凋亡的作用可能与促凋亡因子Caspase-8的上调相关。     

基于DNA的无机纳米材料组装

纳米材料由于其独特的光、热、电、磁学性质,已数年持续成为研究热点.而生物分子,包括多肽、核酸适配体、蛋白质以及DNA,与纳米材料间的相互作用也引起了国内外研究工作者的持续关注.而利用生物分子的高度选择性和特异性来诱导纳米材料组装,对于构建纳米结构单元的器件和实现纳米材料的周期性组装,成为获得有序的纳米结构最为有效的方法之一[1],也已经成为纳米科技领域所面临的巨大挑战[1-3].     

DNA和蛋白质相互作用的体外研究方法（下）

Ⅲ.凝胶阻滞分析 一、原理 DNA片段在聚丙烯酰胺凝胶电泳中有一定的迁移率,而在一定条件下,DNA片段与某些蛋白质结合后,在聚丙烯酰胺凝胶电泳中迁移率降低,经X-光片感光后,可以看到     

DNA和蛋白质相互作用的体外研究方法（一）

基因表达的调控是复杂生命现象的基础和根本所在,这一研究领域已成为生命科学的前沿。世界上许多著名实验室都竞相从事这方面的研究。在一定意义上,在这一领域中的研究水平代表一个国家或一个单位在生命科学研究中的水平和地位。 基因表达的调控是一个多层次、多因素和具有时空特点的协同作用过程。就分子水平而言,涉及核酸-核酸相互作用、蛋白质-蛋白质相互作用、蛋白质-核酸相互作用等主要的作用。目前,顺式调控元件的结构与功能、反式作用因子的结构与功能及调控元件与反式作用因子的相互作用等是研究的热点,并已取得进展。 为了帮助广大读者和生命科学工作者了解和开展相关工作,我们将陆续组织与之相关的技术和方法学介绍。本期发表张永莲教授一文,因篇幅较长,将分两次刊登。欢迎有关专家来稿。     

DNA病毒与RNA病毒相互作用小鼠模型的建立

用Ｃ型病毒（ＲＮＡ病毒）和／或紫外线灭活的（疱疹病毒）ＨＳＶ－２（Ｗｕ）或ＨＳＶ－２（３３３）接种新生小鼠，结果表明接种了ＨＳＶ－２（Ｗｕ）、ＨＳＶ－２（３３３）和作为对照的小鼠均未发生白血病，在ＨＳＶ－２（Ｗｕ）组中接种了Ｃ型病毒加ＨＳＶ－２（Ｗｕ）的小鼠白血病发生率是７５００％，只接种了Ｃ型病毒的小鼠中有４４．７４％发生白血病，两者之间有高度显著性差异（Ｐ＜０．０１）。另外，在ＨＳＶ－２（３３３）组中用Ｃ型病毒加ＨＳＶ－２（３３３）接种小鼠以后有７９．１６％发生了白血病，只接种了Ｃ型病毒的小鼠中有４１．０２％发生白血病，其差异也有高度显著性（Ｐ＜０．０１）。由此可见Ｃ型病毒分别与ＨＳＶ－２（Ｗｕ）或ＨＳＶ－２（３３３）在诱发小鼠白血病过程中存在相互作用。此动物模型可用于研究两类不同病毒相互作用的致癌原理。     

原子力显微镜在DNA和蛋白质相互作用方面的研究进展

评述了原子力显微镜在研究DNA和蛋白质相互作用领域的应用进展。AFM可在空气和液体中对静态的DNA-protein复合体进行成像,也可在液体中实时观察DNA和protein的反应过程。而且,力模式AFM还可获得DNA和protein分子间作用力的信息。AFM已揭示了许多基因调控的机制,也必将在生命科学的研究中起到越来越重要的作用。     

Interaction of Complement-Solubilized Immune Complexes with CR1 Receptors on Human Erythrocytes. The Binding Reaction

The binding of complement (C)-solubilized ¹²⁵I bovine serum albumin (BSA) anti-BSA immune complexes (IC) to CR1 receptors on human red blond cells (RBC-CR1) was studied. The binding of IC to CRI was strongly dependent on the molar antigen lo antibody ratio, and IC formed in moderate antigen excess showed no binding. IC solubilized, in 50% human serum in the presence of autologous RBC bound rapidly lo RBC-CRI, with maximal binding within less than 1 min at 37°C. Release of CRI-hound IC under these conditions occurred slowly, requiring more than.30 min. Only binding of 'partially' solubilized, e.g., anti C3c (C4c) and conglutinin-reactive 1C occurred, whereas fully solubilized complexes (IC-C3dg. C4d) showed virtually no binding. Solubilization of IC in the presence of Mg-EGTA or in C2-deficient serum resulted in a markedly delayed binding of IC ti RBC, indicating the importance of an intact classical pathway in preparing the IC for binding to RBC-CR1. C-solobilized IC could be absorbed to solid-phase conglutinin or antibody to C3c abd C4c, and tgese kugabds were able to inhibit the binding of solubilized IC to RBC. Heparin also exerted a marked, dose-dependent inhibitory effect on the binding of presolubilized IC to RBC-CR1, whereas the binding was unaffected by the addition of monosaccharides or by the concentration of Ca²⁻ or Mg²⁻ ions.     

Problems in the Measurement of Putative Serum Immune Complexes by the Method of Beaumont

ABSTRACT: A methodological investigation of the procedure used by Beaumont et al for measuring a “serum immune complex” precipitated by 25% ammonium sulfate and alleged to contain an ethynyl-estradiol binding immunoglobulin has found major problems with reproducibility and with the correlation of total protein as measured by the Lowry method and the IgG content as determined by a specific nephelometric procedure.     

On the Interaction of the First Complement Component C1 and its Subunit Clq with Solid-Phase IgM Immune Complexes

The interaction of C1 and C1q with solid-phase anti-dextran MOPC-104E IgM was studied. An enzyme-linked immunosorbent assay (ELISA) was used to detect bound C1q. The results revealed that immobilized IgM is converted to the functionally active 'staple' conformation by the specific polyvalent ligand dextran (B 1355/S). C1q is fixed to IgM dependent on the antigen concentration, and its binding might be explained by assuming a functional binding constant (K) of approximately 10(9) M-1. Molecules bound with a K in the range of 10(7) M-1 cannot be detected by this ELISA procedure. The fixation of C1q saturated with an excess of the C1r2S2-tetramer differs from that of free C1q. C1q incorporated in the C1 complex rapidly dissociates independently of the antigen concentration. Since the complement binding sites are located at definite positions on the IgM molecule because of its pentameric structure, it is suggested that the distinguishable association properties of C1 and C1q are brought about from the altered flexibility of the C1q molecule complexed with C1r2S2.     

Transition Metal Complexes as Catalysts for the Homo‐ and Copolymerisation of Olefins and Non‐Conjugated Dienes

The copolymerisation of ethylene with 5,7‐dimethylocta‐1,6‐diene (5,7‐DMO) was conducted in the presence of a series of catalytic systems, based on different transition metal derivatives associated with methylaluminoxane (MAO): a metallocene‐based catalyst, Cp₂ZrCl₂ (1) ; a constrained geometry catalyst (Me₄Cp)SiMe₂(N‐tert‐Bu)TiCl₂ (2) ; an iron‐based catalyst, [(ArN=C(Me))₂C₅H₃N]FeCl₂ (3) ; and a Brookhart‐type catalyst [Ar—N=C(An)C(An)=N—Ar]NiBr₂ (Ar = 2‐C₆H₄(t‐Bu)) ( 4 ). The metallocene catalyst (1) and the constrained geometry catalyst (2) are able to incorporate 5,7‐dimethylocta‐1,6‐diene (5,7‐DMO) into polyethylene chains. Although (2) shows lower overall activities than Cp₂ZrCl₂, similar 5,7‐DMO incorporation levels are obtained for much lower diene concentrations in the feed. The characteristics of the copolymers obtained with the two catalysts are compared. The iron catalyst (3) can only homopolymerise ethylene. However, the presence of 5,7‐DMO in the feed does not significantly affect the polymerisation activity. On the contrary, with the Brookhart system (4) , the presence of 5,7‐DMO as well as any of the tested dienes (5‐ethylidene‐2‐norbornene, 7‐methyl‐1,6‐octadiene and 1,5‐hexadiene) completely inhibits the polymerisation of olefins. A tentative mechanism, based on the chain migration mechanism proposed by Brookhart is suggested for the deactivation of the Ni catalyst.     

Interaction of a Serum Inhibitor of C′1-Esterase with Intermediate Complexes of the Immune Haemolytic System: II. Kinetics and Mechanism of the Interaction*

The kinetics of the reaction between C′1-esterase inhibitor and an intermediate complex of sensitized sheep erythrocytes and human complement are described. The rate of reaction was directly proportional to the concentrations of both inhibitor and intermediate complex, but was insensitive to changes in pH over the range 7.4–8.7 and in ionic strength from 0.15–0.24. The rate of reaction was accelerated by an increase in temperature over the range 22°–37°. The experimental evidence was consistent with a mechanism picturing the reaction of C′1-esterase inhibitor with C′1-esterase bound to the intermediate complex. A theoretical treatment is described from which values for various kinetic and thermodynamic quantities may be calculated.     

成人干桡骨有机质和无机质的含量

本文是将１０个成人干桡骨分别等分为１６段，以骨段为单位研究桡骨内有机质和无机质的含量。结果如下：（１）１６０个骨段平均含有机质３６．２３％，无机质６３．７７％；（２）桡骨近侧端和远侧端有机质的含量明显地高于其它骨段的含量（Ｐ＜０．０５）；（３）桡骨骨干各段的无机质含量明显地高于骨两端的含量（Ｐ＜０．０５）；（４）骨干各相邻骨段之间的无机质含量无显著性差异（Ｐ＞０．２）；（５）第１４段骨的无机质含量明显地高于第１５段骨的无机质含量（Ｐ＜０．０２）．第１４段骨距桡骨下端２．８６－４．２ｃｍ，正好位于Ｃｏｌｌ’ｓ骨折常见的发生部位，该部位的这一结构特点可能是桡骨下段易于发生骨折的原因之一。     

Human Amoebiasis: The Interaction of Lymphocyte Surface-Bound Immune Complexes and Pmns Impairs T Cell Proliferative Responses to E. Histolytica Mitogen

In some of the sera from patients with amoebiasis circulating immune complexes are present which are thought to interact with lymphoid cells, enabling them to elicit a burst of oxygen consumption in PMNs. The intensity of chemiluminescence is related to the presence of C3⁺ and Fc IgG⁺ cells in the lymphoid cell suspensions employed. The generation and release of highly reactive oxygen derivatives from PMNs impair T lymphocyte proliferative responses to the E. histolytica mitogen. The Authors suggest that one of the mechanisms by which circulating immune complexes present in the sera of patients with amoebiasis may interfere with T cell-mediated immune responses, is through their binding to the surface of the C3⁺, Fc IgG⁺ cells with subsequent stimulation of the PMN oxidative metabolism.