共查询到20条相似文献,搜索用时 455 毫秒
1.
2.
应用光谱法研究了生物大分子探针型主体分子罗丹明B-β-环糊精衍生物与DNA的相互作用及温度对该探针特性的影响,探讨了相应的主体分子与DNA分子相互作用的方式,嵌插作用能力大小以及温度对主体分子含客体分子时的影响,进一步研究了探针型主-客体分子相互识别作用及作用能力的大小,探讨了主-客体分子相互识别作用的机制。 相似文献
3.
核酸修饰电极研究进展 总被引:9,自引:0,他引:9
介绍了核酸修饰电极的制备及其特点,对核酸修饰电极用于NA的痕量分析,电化学DNA传感器,NA与其它分子相互作用,以及NA的结构研究等方面的最新进展进行了评述。 相似文献
4.
在石墨电极上脱氧核糖核酸与米托蒽醌嵌入作用的电化学研究 总被引:11,自引:0,他引:11
本文研究了单链DNA分子在石墨电上的固定方法,采用核酸分子杂交技术,使具有电化学活性的米托蒽酯嵌入DNA分子双螺旋结构的碱基对中,在电极上形成dsDNA-MS层,通过伏安法研究DNA分子和MX相互作用的电化学行为。 相似文献
5.
6.
许多重要的生物过程的调节都通过蛋白-蛋白相互作用来实现的。一般,蛋白-蛋白作用的界面太大而不能被小分子药物选择性靶向,因此小分子药物很难高效特异性地阻断该类型的相互作用。此外,由于蛋白质药物很难透过细胞膜,它们也不能直接靶向细胞内的相互作用。由于当前药物分子的限制,发展下一代既能进入细胞膜又能特异性靶向蛋白-蛋白相互作用的分子成为新的研究热点。为了克服上述药物分子的缺点,Verdine等发展了一种全碳支架的具有α-螺旋结构的新型多肽,这种多肽被称作订书肽(stapled peptides)。相比于天然多肽,订书肽有更高的酶解稳定性并且可以进入细胞膜,从而提高了它的药理性能。本文将从订书肽的化学合成、生物物理性能的表征和其在癌症和HIV治疗、信号通路的调节和肿瘤激活蛋白的抑制方面的生物应用详细介绍订书肽的最新进展。 相似文献
7.
8.
不可逆电活性药物米托蒽醌与脱氧核糖核酸的相互作用 总被引:4,自引:0,他引:4
研究了抗癌新药米托蒽醌(MXT)的电化学行为及与脱氧核糖核酸(DNA)的相互作用,推导了适用于研究不可逆电活性分子与DNA相互作用的电化学公式,运用该公式可以简便、快速地测定靶向分子与DNA的结合常数和结合位点数。实验发现,MXT与小牛胸腺DNA的结合以蒽醌母核的嵌插作用为主,同时,烃氨基侧链与骨架磷酸基团之间的静电吸引对母核起稳定作用,使化合物易于嵌入DNA的平面结构。MXT与DNA相互作用引起的峰电流的变化可以用于分析测定DNA。 相似文献
9.
蛋白质是生命功能的执行者,其功能的发挥受自身结构动态变化、与其他生物分子的相互作用及修饰等因素的调节。因此,对蛋白质及蛋白复合物结构的研究有助于揭示重要生命过程中的分子机理与机制。氢氘交换质谱(Hydrogen deuterium exchange mass spectrometry,HDX-MS)是研究蛋白质结构、动态变化和相互作用的强有力工具,也是传统生物物理手段的重要补充。该文综述了HDX-MS的基本原理、机制、实验方法和研究最新进展,并从蛋白质自身动态变化、蛋白质-小分子相互作用、蛋白质-蛋白质相互作用3个方面介绍了近年来HDX-MS在蛋白及蛋白复合物研究中的应用进展。 相似文献
10.
11.
Stephen Neidle 《Chemical record (New York, N.Y.)》2015,15(4):691-710
The story behind some of the early studies in the laboratory of Stephen Neidle on quadruplex‐binding small molecules and the structural studies on quadruplexes and their complexes is presented and discussed in the context of his earlier work on drug–DNA interactions. More recent studies and future directions in the rational design of small molecules targeting telomeric and gene promoter quadruplexes are also described. 相似文献
12.
Single‐molecule force spectroscopy (SMFS) opens new avenues for elucidating the structures and functions of large coiled molecules such as synthetic and biopolymers at the single‐molecule level. In addition, some of the features in the force–extension curves (i.e. force spectra) are closely related to primary/secondary structures of the molecules being stretched. For example, the long force plateau in the DNA stretching curve is related to the double‐helix structure. These features can be regarded as the force fingerprints of individual macromolecules. These force fingerprints can therefore be used as indicators/criteria of single‐molecule manipulation during the measurement of some unknown intra‐ or intermolecular interactions. By comparing the force spectra of a single polymer chain before and after interaction with other molecules, the mode/strength of such molecular interactions can be derived. This Review focuses on recent advances in AFM‐based SMFS studies on molecular interactions in both synthetic and biopolymer systems using a single macromolecular chain as probe, including interactions between nucleic acids and proteins, mechanochemistry of covalent bonds, conformation‐regulated enzymatic reactions, adsorption and desorption of biopolymers on a flat surface or from the nanopore of a carbon nanotube, and polymer interactions in the condensed state. 相似文献
13.
Ladame S Schouten JA Stuart J Roldan J Neidle S Balasubramanian S 《Organic & biomolecular chemistry》2004,2(20):2925-2931
3,6-Bis-peptide acridine and acridone conjugates have been designed and synthesised to selectively interact with G-quadruplex DNA. The ligand properties are peptide sequence dependent, the highest discrimination being obtained with the FRHR tetrapeptide (up to >50-fold specificity). Molecular modeling studies have helped us rationalise the data and suggest that human telomeric quadruplex DNA can readily accommodate tetrapeptides, and furthermore that FRHR contributes to stabilization of the complex by non-bonded interactions within the TTA loop pockets of the quadruplex. These studies indicate that targeting distinct features of a G-quadruplex with hybrid molecules is a promising strategy for discriminating between quadruplex and duplex DNA. 相似文献
14.
Bioactive Structure of Membrane Lipids and Natural Products Elucidated by a Chemistry‐Based Approach 下载免费PDF全文
Michio Murata Shigeru Sugiyama Shigeru Matsuoka Nobuaki Matsumori 《Chemical record (New York, N.Y.)》2015,15(4):675-690
Determining the bioactive structure of membrane lipids is a new concept, which aims to examine the functions of lipids with respect to their three‐dimensional structures. As lipids are dynamic by nature, their “structure” does not refer solely to a static picture but also to the local and global motions of the lipid molecules. We consider that interactions with lipids, which are completely defined by their structures, are controlled by the chemical, functional, and conformational matching between lipids and between lipid and protein. In this review, we describe recent advances in understanding the bioactive structures of membrane lipids bound to proteins and related molecules, including some of our recent results. By examining recent works on lipid‐raft‐related molecules, lipid–protein interactions, and membrane‐active natural products, we discuss current perspectives on membrane structural biology. 相似文献
15.
应用紫外光谱、荧光探针、zeta 电位、动态光散射和凝胶电泳等方法探讨了阳离子gemini 表面活性剂C12H25N+(CH3)2―(CH2)6―(CH3)2N+C12H25·2Br-(12-6-12)与DNA之间的相互作用. 研究结果表明, 与传统表面活性剂相比, 偶联表面活性剂特殊的分子结构使其与DNA的作用更强烈. DNA引导表面活性剂在其链周围形成类胶束结构, 开始形成类胶束时对应的表面活性剂临界聚集浓度(CAC)比纯表面活性剂临界胶束浓度(CMC)低两个数量级. CAC与DNA的浓度无关, 而与表面活性剂之间的疏水作用以及表面活性剂与DNA之间的静电吸引作用密切相关. Zeta 电位和凝胶电泳结果显示了DNA链所带负电荷逐渐被阳离子表面活性剂中和的过程. 借助原子力显微镜(AFM)成功观察到了松散的线团状DNA, 球状体随机地分散在DNA链上形成类似于串珠的结构、尺寸较大的球形复合物以及其由于吸附多余的表面活性剂重新带正电而被溶解得到的较小DNA/12-6-12聚集体. 圆二色(CD)光谱结果显示, 12-6-12可以诱导DNA的构象发生改变. 相似文献
16.
Sugar–Edge Interactions in a DNA–RNA G‐Quadruplex: Evidence of Sequential C−H⋅⋅⋅O Hydrogen Bonds Contributing to RNA Quadruplex Folding 下载免费PDF全文
Jonathan Dickerhoff Dr. Bettina Appel Prof. Dr. Sabine Müller Prof. Dr. Klaus Weisz 《Angewandte Chemie (International ed. in English)》2016,55(48):15162-15165
DNA G‐quadruplexes were systematically modified by single riboguanosine (rG) substitutions at anti‐dG positions. Circular dichroism and NMR experiments confirmed the conservation of the native quadruplex topology for most of the DNA–RNA hybrid structures. Changes in the C8 NMR chemical shift of guanosines following rG substitution at their 3′‐side within the quadruplex core strongly suggest the presence of C8?H???O hydrogen‐bonding interactions with the O2′ position of the C2′‐endo ribonucleotide. A geometric analysis of reported high‐resolution structures indicates that such interactions are a more general feature in RNA quadruplexes and may contribute to the observed preference for parallel topologies. 相似文献
17.
Research into the interactions of small molecules (ligands) with DNA is a very important field of biochemistry. A ligand interacts
with a DNA structure in many ways, depending on the structural features of the ligand (the presence of rings, substituent
groups, length of bonds, etc.) or nucleic acid (number and association of strands, base sequence etc.). This study reports
on an investigation of the preferential binding of arylstilbazolium ligands to a four-stranded DNA. For this purpose, an equilibrium
dialysis was used. Equilibrium dialysis is a versatile method which enables many DNA structures to be investigated at the
same time. A dozen different DNA structures of (single-stranded, double-stranded (duplex), triple-stranded (triplex), and
four-stranded (tetraplex)) were involved in experiments with each ligand. Following the dissociation of DNA-ligand complexes
by SDS, the concentration of the ligand bound was calculated from fluorescence and absorbance calibration curves. As a result,
the amount of the ligand bound was directly related to the ligand-binding affinity. Equilibrium dialysis was used as a powerful
tool to indicate which of the arylstilbazolium ligands investigated was the best therapeutic agent targeting G-quadruplex.
Arylstilbazolium derivatives demonstrated strong interactions with the DNA samples used in the assay. The most interesting
finding was a selective, preferential binding of anthryl derivative to c-MYC DNA (c-MYC is a DNA sequence that appears in
an oncogene). Furthermore, as this derivative binds preferentially to one of the triplexes investigated, it can find an application
in the TFO-triplex forming oligonucleotides which are used in gene therapy. 相似文献
18.
Prof. Fumi Nagatsugi Ass. Prof. Kazumitsu Onizuka 《Chemical record (New York, N.Y.)》2023,23(2):e202200194
DNA and RNA can adopt a variety of stable higher-order structural motifs, including G-quadruplex (G4 s), mismatches, and bulges. Many of these secondary structures are closely related to the regulation of gene expression. Therefore, the higher-order structure of nucleic acids is one of the candidate therapeutic targets, and the development of binding molecules targeting the higher-order structure of nucleic acids has been pursued vigorously. Furthermore, as one of the methodologies for detecting the higher-order structures of these nucleic acids, developing techniques for the selective chemical modification of the higher-order structures of nucleic acids is also underway. In this personal account, we focus on the following higher-order structures of nucleic acids, double-stranded DNA containing the abasic site, T−T/U−U mismatch structure, and G-quadruplex structure, and describe the development of molecules that bind to and chemically modify these structures. 相似文献
19.
Zhao X Liu X Wang Y Chen Z Kang L Zhang H Luo X Zhu W Chen K Li H Wang X Jiang H 《Journal of chemical information and modeling》2008,48(7):1438-1447
An improved potential mean force (PMF) scoring function, named KScore, has been developed by using 23 redefined ligand atom types and 17 protein atom types, as well as 28 newly introduced atom types for nucleic acids (DNA and RNA). Metal ions and water molecules embedded in the binding sites of receptors are considered explicitly by two newly defined atom types. The individual potential terms were devised on the basis of the high-resolution crystal and NMR structures of 2,422 protein-ligand complexes, 300 DNA-ligand complexes, and 97 RNA-ligand complexes. The optimized atom pairwise distances and minima of the potentials overcome some of the disadvantages and ambiguities of current PMF potentials; thus, they more reasonably explain the atomic interaction between receptors and ligands. KScore was validated against five test sets of protein-ligand complexes and two sets of nucleic-acid-ligand complexes. The results showed acceptable correlations between KScore scores and experimentally determined binding affinities (log K i's or binding free energies). In particular, KScore can be used to rank the binding of ligands with metalloproteins; the linear correlation coefficient ( R) for the test set is 0.65. In addition to reasonably ranking protein-ligand interactions, KScore also yielded good results for scoring DNA/RNA--ligand interactions; the linear correlation coefficients for DNA-ligand and RNA-ligand complexes are 0.68 and 0.81, respectively. Moreover, KScore can appropriately reproduce the experimental structures of ligand-receptor complexes. Thus, KScore is an appropriate scoring function for universally ranking the interactions of ligands with protein, DNA, and RNA. 相似文献
20.
Sandra Ramotowska Aleksandra Ciesielska Mariusz Makowski 《Molecules (Basel, Switzerland)》2021,26(11)
The interactions of compounds with DNA have been studied since the recognition of the role of nucleic acid in organisms. The design of molecules which specifically interact with DNA sequences allows for the control of the gene expression. Determining the type and strength of such interaction is an indispensable element of pharmaceutical studies. Cognition of the therapeutic action mechanisms is particularly important for designing new drugs. Owing to their sensitivity, simplicity, and low costs, electrochemical methods are increasingly used for this type of research. Compared to other techniques, they require a small number of samples and are characterized by a high reliability. These methods can provide information about the type of interaction and the binding strength, as well as the damage caused by biologically active molecules targeting the cellular DNA. This review paper summarizes the various electrochemical approaches used for the study of the interactions between pharmaceuticals and DNA. The main focus is on the papers from the last decade, with particular attention on the voltammetric techniques. The most preferred experimental approaches, the electrode materials and the new methods of modification are presented. The data on the detection ranges, the binding modes and the binding constant values of pharmaceuticals are summarized. Both the importance of the presented research and the importance of future prospects are discussed. 相似文献