基于金属的神经退行性疾病治疗策略

本文综述了金属离子在神经退行性疾病中的重要作用以及针对该类疾病金属治疗药物的研究进展。以老年痴呆症和帕金森氏症为代表,结合本课题组的初步研究结果,讨论了金属离子在蛋白质聚集与氧化应激反应中的重要作用,暗示金属螯合策略应成为治疗该类疾病的首选策略,并介绍了数种已用于或即将用于临床实验的金属螯合制剂;还介绍了烷基化神经退行性疾病相关蛋白的金属结合位点,可以显著抑制该蛋白质聚集体的形成和活性氧的产生,这可能是继螯合策略后一种更有发展潜力的神经退行性疾病治疗方法。     

神经生物系统中的配位化学问题

从上个世纪末开始，金属离子在神经生物系统中的作用受到了广泛的关注。生物学家开始注意到一些重要生理过程中金属离子的化学及生物化学问题。本文总结了近年来在该领域的最新研究进展，并着重介绍了过渡金属离子与神经退行性疾病之间的联系。     

姜黄素抑制金属离子诱导的丝素蛋白构象转变及其作用机理

以丝素蛋白(SF)为神经退行性疾病相关蛋白的模型蛋白,分析了姜黄素(Curcumin)对Zn(Ⅱ)和Cu(Ⅱ)离子诱导的丝素蛋白构象转变的干预作用及其作用机理,试图探讨姜黄素在神经退行性疾病中的预防与治疗作用.结果表明,姜黄素可通过与Cu(Ⅱ)和Zn(Ⅱ)离子络合,干预金属离子诱导的丝素蛋白构象转变,并且所形成的络合物Cu(Ⅱ)-Curcumin可抑制丝素蛋白的构象转变,但是Zn(Ⅱ)-Curcumin络合物不具有这种能力.因此,基于姜黄素对于金属离子诱导的丝素蛋白构象转变具有良好的干预作用,可以将姜黄素作为神经退行性疾病预防和治疗的潜在候选药物.     

青霉素-金属相互作用研究进展

金属离子可以影响许多药物分子的稳定性、体内分布和代谢途径以至于影响药物的活性.青霉素这种由细菌产生的天然物质是一类重要而有发展前途的β-内酰胺药物。一些过     

蛇毒蛋白质中金属离子及其配位化学的研究

蛇毒蛋白质中金属离子及其配位化学的研究刘清亮吴双顶张祖德余华明（中国科学技术大学应用化学系安徽合肥２３００２６）在生命体内，金属离子能参与许多重要的生物化学反应，其实质就是金属离子与生物大分子的相互作用。蛇毒可以用作药物，具有抗凝、止血、抗癌和镇痛等...     

用于肿瘤诊疗的金属-多酚网络多功能材料

多酚广泛存在于自然界的各种植物中,具有抗癌、抗血栓以及其他保健功效。金属离子在生物和化学催化领域以及各种疾病的检测和治疗中起着非常重要的作用。金属离子和多酚能方便快捷地自组装成金属-多酚网络,其简单绿色的组装制备过程以及对各种实体表面的黏附特性使其在仿生学、材料学和生物医学等领域凸显出巨大的应用潜力。本文总结了近年来金属-多酚类纳米材料在生物医用方面的探索和应用,介绍了本课题组关于金属-多酚网络在肿瘤诊疗方面的研究工作,并对金属-多酚类纳米材料的发展趋势进行了展望。     

聚丙烯酰胺凝胶电泳-化学发光成像技术检测血清中的蛋白与药物的结合

血清蛋白分析是临床检验的一项重要的任务,血清中各种蛋白的指认和分析对于疾病的治疗和药物的研究具有重要的意义.药物在人血清中的分布和药物与血清蛋白的结合程度,使得药物的最大作用强度、作用幅度以及作用时间不同,最终导致了药效的不同.     

金属蛋白研究中几个值得注意的动向

本文叙述了金属蛋白和金属酶研究中近年来几个值得注意的发展动向，即与金属离子相关的疾病（特别是神经退行性疾病）、金属离子在蛋白质的折叠、聚集和装配中的作用，金属伴侣分子、金属蛋白的设计和构建、金属蛋白与DNA相互作用。     

过渡金属离子与神经退行性疾病

介绍过渡金属离子在神经退行性疾病中的作用和生物学意义,以及一种可能的金属作用下的神经退行性疾病致病机理。重点介绍铜离子在老年痴呆症、家族性肌萎侧索硬化症、克雅氏症等疾病的致病机理方面的作用。     

我国生物无机化学的发展

叙述了生物无机在我国的发展。着重从金属离子及其配合物与生物大分子的作用、药物中的金属及抗癌活性配合物的作用机理、稀土元素生物无机化学、金属离子与细胞的作用、金属蛋白与金属酶、生物矿化、环境生物无机化学等七个方面综述了我国已取得的进展和成绩。     

Mechanism of DNA-drug interactions

Over the last two decades many strategies have been planned to design specific drugs for rare diseases to target their action at the DNA level. Advancements in our understanding of the interactions of small nonpeptide molecules with DNA have opened the doors for “rational” drug design. Special methods have now been developed to give accurate account of the precise location of ligand-DNA adducts on target DNA. We are now in a position to think of designing ligands that recognize particular sequences of base pairs. This work will allow us to enter into a new era of gene therapy for diseases like Cystic fibrosis, Alzheimer’s disease and many related disorders at genetic level. These ligands can also be employed in the treatment of various types of cancers. They may also be useful as highly specific probes to locate particular sequences in the genomic DNA.     

基于DNA纳米结构的细胞间相互作用的调控

细胞通过化学信号、 电子交换和直接接触等方式交换彼此之间的物质和信息, 以调节生命体的生长发育. 因此, 细胞间的相互作用研究与调控在细胞功能的机制研究和疾病的诊断及治疗等领域具有非常重要的意义. DNA纳米结构具有易合成、 易修饰、 可编程性设计及生物安全性高等优点, 有望实现操作简单、 精确可调、 智能响应的细胞间相互作用调控, 受到了广泛关注. 本文综述了寡核苷酸链杂交、 受体-配体结合和核酸适体靶向识别等基于DNA纳米结构的细胞组装策略, 总结了pH调控、 金属离子调控和DNA链激活等细胞间相互作用的调控手段, 并重点介绍了其在细胞间作用力的测量和成像、 体外组织模型的构建、 细胞间的通讯交流和细胞免疫治疗等领域的应用. 最后对该领域进行了总结和展望, 希望为相关研究提供有益参考.     

Nanomaterial‐based Sensors for the Study of DNA Interaction with Drugs

The interaction of drugs with DNA has been searched thoroughly giving rise to an endless number of findings of undoubted importance, such as a prompt alert to harmful substances, ability to explain most of the biological mechanisms, or provision of important clues in targeted development of novel chemotherapeutics. The existence of some drugs that induce oxidative damage is an increasing point of concern as they can cause cellular death, aging, and are closely related to the development of many diseases. Because of a direct correlation between the response, strength/ nature of the interaction and the pharmaceutical action of DNA‐targeted drugs, the electrochemical analysis is based on the signals of DNA before and after the interaction with the DNA‐targeted drug. Nowadays, nanoscale materials are used extensively for offering fascinating characteristics that can be used in designing new strategies for drug‐DNA interaction detection. This work presents a review of nanomaterials (NMs) for the study of drug‐nucleic acid interaction. We summarize types of drug‐DNA interactions, electroanalytical techniques for evidencing these interactions and quantification of drug and/or DNA monitoring.     

DNA与其靶向分子相互作用研究进展

ＤＮＡ与其靶向分子相互作用的研究不仅对阐述一些抗肿瘤,抗病毒药物及致癌物的作用机理。而且对进一步指导人工核酸酶的合成及ＤＮＡ高级结构等方面的工作都具有重要意义。本文着重评述了近年来不同结构类型的ＤＮＡ靶向分子与ＤＮＡ相互作用研究方面的进展。     

Magnetic beads as versatile tools for electrochemical DNA and protein biosensing

Magnetic beads (MBs) are versatile tools in the separation of nucleic acids, proteins and other biomacromolecules, their complexes and cells. In this article recent application of MBs in electrochemical biosensing and particularly in the development of DNA hybridization sensors is reviewed. In these sensors MBs serve not only for separation but also as a platform for optimized DNA hybridization. A hybridization event is detected separately at another surface, which is an electrode. The detection is based either on the intrinsic DNA electroactivity or on various kinds of DNA labeling, including chemical modification, enzyme tags, nanoparticles, electroactive beads, etc., greatly amplifying the signals measured. In addition to DNA hybridization, other kinds of biosensing in combination with MBs, such as DNA-protein interactions, are reviewed.     

Fluorescent small molecule probe to modulate and explore α2β1 integrin function

Collagen binding integrins are an important family of cell surface receptors that mediate bidirectionally signals between the interior of the cell and the extracellular matrix. The protein-protein interactions between cells and collagen are necessary for many physiological functions, but also promote diseases. For example, the interaction of α2β1 integrin and collagen has been shown to have an important role in thrombus formation and cancer spread. The fact that the discovery of small molecules that can block such protein-protein interactions is highly challenging has significantly hindered the discovery of pharmaceutical agents to treat these diseases. Here, we present a rationally designed novel fluorescent molecule that can be synthesized in just a few minutes from commercially available starting materials. This molecule blocks the protein-protein interaction between α2β1 integrin and collagen, and due to its fluorescent properties, it can be employed in wide variety of biological applications.     

Homology modeling,docking and structure-based pharmacophore of inhibitors of DNA methyltransferase

DNA methyltransferase 1 (DNMT1) is an emerging epigenetic target for the treatment of cancer and other diseases. To date, several inhibitors from different structural classes have been published. In this work, we report a comprehensive molecular modeling study of 14 established DNTM1 inhibitors with a herein developed homology model of the catalytic domain of human DNTM1. The geometry of the homology model was in agreement with the proposed mechanism of DNA methylation. Docking results revealed that all inhibitors studied in this work have hydrogen bond interactions with a glutamic acid and arginine residues that play a central role in the mechanism of cytosine DNA methylation. The binding models of compounds such as curcumin and parthenolide suggest that these natural products are covalent blockers of the catalytic site. A pharmacophore model was also developed for all DNMT1 inhibitors considered in this work using the most favorable binding conformations and energetic terms of the docked poses. To the best of our knowledge, this is the first pharmacophore model proposed for compounds with inhibitory activity of DNMT1. The results presented in this work represent a conceptual advance for understanding the protein–ligand interactions and mechanism of action of DNMT1 inhibitors. The insights obtained in this work can be used for the structure-based design and virtual screening for novel inhibitors targeting DNMT1.     

过氧亚硝酸根对蛋白质损伤的研究进展

过氧亚硝酸根--一氧化氮和超氧根阴离子快速结合的产物，是生物体内产生的一种强氧化剂和细胞毒性物质，它可以介导生物大分子包括DNA、蛋白质和脂质的修饰和损伤。近年来，由于许多疾病条件下都发现大量过氧亚硝酸根诱导的蛋白质损伤产物，因此过氧亚硝酸根与蛋白质的相互作用引起了人们的广泛关注。本文详尽地介绍了过氧亚硝酸根介导蛋白质损伤对人体的病理作用和过氧亚硝酸根与蛋白质作用机制等方面的最新研究进展，并对未来过氧亚硝酸根与蛋白质相互作用的研究作了展望。