Electrospray ionization mass spectrometry of oligonucleotide complexes with drugs, metals, and proteins.

I. Introduction 61 II. Binding of Small Molecules to DNA 62 A. Covalent Binding 62 B. Reversible (Noncovalent) DNA-Binding Agents 65 III. DNA-Metal Ion Complexes 67 A. Platinum Complexes 70 B. Other Metal Ions 73 IV. DNA-Protein Complexes 74 A. Introduction 74 B. ESI-MS of DNA-Protein Complexes 76 C. ESI-MS Analysis of Proteolytic Products of DNA-Protein Complexes 79 D. ESI-MS of Ternary DNA-Protein-Ligand Complexes 80 V. Conclusions 80 Abbreviations 81 References 81 --Interactions of DNA with drugs, metal ions, and proteins are important in a wide variety of biological processes. With the advent of electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI), mass spectrometry (MS) is now a well-established tool for the characterization of the primary structures of biopolymers. The gentle nature of the ESI process, however, means that ESI-MS is also finding application for the study of noncovalent and other fragile biomolecular complexes. We outline here the progress, to date, in the use of ESI-MS for the study of noncovalent drug-DNA and protein-DNA complexes together with strategies that can be employed to examine the binding of small molecules and metal complexes to DNA. In the case of covalent complexes with DNA, sequence information can be derived from ESI-MS used in conjunction with tandem mass spectrometry (MS/MS) and/or enzymatic digestion. MS/MS can also be used to probe the relative binding affinities of drugs that bind to DNA via noncovalent interactions. Overall, the work in this area, to date has demonstrated that ESI-MS and MS/MS will prove to be valuable complements to other structural methods, offering advantages in terms of speed, specificity, and sensitivity. (c) 2001 John Wiley & Sons, Inc.     

电喷雾质谱在超分子体系中非共价相互作用研究中的应用

作为研究非共价复合物的有力工具 ,近年来电喷雾质谱被越来越多地应用于研究超分子体系中的非共价相互作用。本文较详细地综述了电喷雾质谱法在研究超分子体系中非共价相互作用方面的应用 ,内容涉及结合的选择性、结合常数的测定、结合位点的确定及手性识别等多方面。同时还讨论了相关实验中需注意的控制实验条件和采用离子标记等问题。     

龙胆质谱指纹图谱及化学模式识别方法研究

利用电喷雾质谱(ESI-MS)法建立龙胆质谱指纹图谱,研究其中代表性裂环烯醚萜苷类成分的ESI-MS 规律。采用甲醇超声法提取龙胆中裂环烯醚萜苷类成分,在正离子方式检测模式下直接进样,应用一级全扫描质谱建立其特征图谱。运用化学模式识别方法对图谱数据进行分析,发现秋季龙胆样品的聚集程度优于春季龙胆样品,根据春季、秋季药材样品的差异,可以对采收期进行区分;裂环烯醚萜苷类成分在二级质谱中易发生脱水、乙酰基、葡萄糖基等。电喷雾质谱法的精密度、稳定性、重现性均符合要求,且具有特征性强、分析速度快、样品用量少等优点。     

质谱动力学方法在手性识别及对映体过量值方面的原理及应用

近年来电喷雾质谱被越来越多地应用于手性分析研究中,本工作综述了质谱中的动力学方法在手性识别和对映体过量值测量中的应用,并对该方法在这些主要应用中存在的关键问题进行讨论。动力学方法是通过观察离子键合三元复合物离子的碰撞诱导解离反应,测量一对竞争反应速率常数的比值。当上述离子键合三元复合物由手性配体和手性分析物组成时,速率常数的比值与三元金属复合物中手性分析物的绝对构型有关,这是手性识别和对映体过量值测量的基础。研究中所涉及的手性化合物已经从以往对氨基酸扩展到了手性药物,手性糖等。     

乌头碱类生物碱的质谱研究进展

本文简述质谱方法在乌头碱型 C19二萜生物碱的分析和结构鉴定等方面的应用以及不同电离方式下乌头碱的断裂行为 ,并总结我们近来利用电喷雾串联质谱技术分析几种乌头属植物中生物碱的研究结果 ,提出脂类生物碱 ( lipo-alkaloids)存在于其它乌头属植物中的可能性     

Mass spectrometry for the study of protein glycation in disease

The structural elucidation of advanced glycation end-product (AGE)-modified proteins and quantitative analysis of free AGEs have been successfully performed, by use of mass spectrometry (MS) in plasma and tissues of patients with AGE-related diseases, such as diabetes mellitus, uremia, cataract, and liver cirrhosis. Matrix-assisted laser desorption/ionization (MALDI)-MS made it possible to directly analyze the AGE-modified proteins such as albumin and IgG. However, because the direct structural analysis of intact AGE-modified proteins is often not easy due to the formation of broad and poorly resolved peaks, peptide mapping after enzymatic hydrolysis was introduced into the analysis of AGE-modified proteins and the site-specific analysis of defined AGEs by MALDI-MS. Liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS) has been employed not only for the structural elucidation of enzymatically hydrolyzed AGEs-modified peptides but also for simultaneous quantification of free AGEs in plasma and tissues of patients. Based on many studies that use MS for the analysis of AGEs, there is no doubt as to the important role of protein-linked AGEs in several diseases.     

基于电喷雾质谱的反应监测研究进展

电喷雾质谱(ESI-MS)因具有灵敏度高、响应速度快、分辨率高、原位在线监测等特点,广泛应用于反应监测领域。本文主要从不同离子化技术角度,综述了电喷雾质谱在反应监测和机理研究方面的进展。重点介绍了在线电喷雾质谱技术,其中包括解吸附电喷雾离子化质谱（DESI-MS）、萃取电喷雾离子化质谱（EESI-MS）、纳升电喷雾离子化质谱（nESI-MS）、超声喷雾离子化质谱（SSI-MS）以及其他在线电喷雾离子化质谱在反应监测中的应用。最后,对电喷雾质谱在反应监测的发展趋势进行总结和展望。     

Mass spectrometry in the characterization of reactive metal alkoxides

Metal alkoxides are metal‐organic compounds characterized by the presence of M?O?C bonds (M = metal). Their chemistry seems to be, in principle, relatively simple but the number of possible reactant species arising as a consequence of their behavior is very remarkable. The physico‐chemical properties of metal alkoxides are determined by many different parameters, the most important ones being the electronegativity of the metal, the ramification of the ligand, and the acidity of the corresponding alcohol. Their reactivity makes them suitable and versatile candidates for many applications, including homogeneous catalysis, synthesis of new ceramic materials through the sol‐gel process and, recently, also for Cultural Heritage. Metal alkoxides are characterized by a strong tendency to give clusters and/or oligomers through oxo‐bridges. Mass spectrometry has been successfully employed for the characterization of metal alkoxides in the gas‐phase. Electron ionization (EI) allowed the assessment of the molecular weight and of the most relevant decomposition pathways giving information on the relative bond strength of differently substituted molecules. On the other hand, information on the reactivity in solution of these molecules have been obtained by electrospray ionization (ESI)‐matrix assisted laser desorption ionization (MALDI) experiments performed on their reaction products. These data were relevant to investigate the sol‐gel process. In this review, these aspects are described and the results obtained are critically evaluated. © 2016 Wiley Periodicals, Inc. Mass Spec Rev     

Ionization techniques in capillary electrophoresis-mass spectrometry: principles, design, and application

A major step forward in the development and application of capillary electrophoresis (CE) was its coupling to ESI-MS, first reported in 1987. More than two decades later, ESI has remained the principal ionization technique in CE-MS, but a number of other ionization techniques have also been implemented. In this review the state-of-the-art in the employment of soft ionization techniques for CE-MS is presented. First the fundamentals and general challenges of hyphenating conventional CE and microchip electrophoresis with MS are outlined. After elaborating on the characteristics and role of ESI, emphasis is put on alternative ionization techniques including sonic spray ionization (SSI), thermospray ionization (TSI), atmospheric pressure chemical ionization (APCI), atmospheric pressure photoionization (APPI), matrix-assisted laser desorption ionization (MALDI) and continuous-flow fast atom bombardment (CF-FAB). The principle of each ionization technique is outlined and the experimental set-ups of the CE-MS couplings are described. The strengths and limitations of each ionization technique with respect to CE-MS are discussed and the applicability of the various systems is illustrated by a number of typical examples.     

抗抑郁化合物SIPI5358与α-,β-,γ-环糊精非共价复合物的研究

The non-covalent complexes of α-, β- or γ-cyclodextrin(α-, β- or γ-CD ) with piperazine derivative compound SIPI5358 were investigated by electrospray ionization mass spectrometry(ESI-MS) and UV spectrometry. The mass spectrometry results reveal that SIPI5358(guest) and α-, β- or γ-cyclodextrin(host) can be form 1:1 complexes in solution. The results obtained from ESI-MS are further confirmed by UV spectra.     

电喷雾萃取电离和电喷雾电离所获一价正离子内能差异的比较研究

电喷雾萃取电离（EESI）和电喷雾电离（ESI）均属于软电离技术,但EESI比ESI更温和,能更好地保持蛋白质的构象。本研究以一价正离子为例,分别采用EESI和ESI技术对罗丹明B准分子离子m/z 443的裂解行为进行多级串联质谱研究,考察了不同碰撞能量对裂解行为的影响,建立了这两种离子源产生的离子内能差异（简称内能差异）的定量测定方法,并探讨了该方法的影响因素及适用范围。结果表明,EESI与ESI离子源的内能差异为11.5 eV。该方法可为其他不同离子源产生的离子内能差异比较提供基本思路,也可为深刻理解不同离子源产生离子的质谱行为提供参考。     

小蜡树中苯乙醇苷类化合物的ESI-MS/MS研究

The fragmentation behavior of phenylethanoid glycosides from Fraxinus sieboldiana were investigated systematically by using ESI-MS/MS in negative ion mode. The fragmentation reaction of these compounds is changed according to their different structural type and substitutions. The results of this paper can benefit the rapid determination of phenylethanoid glycosides in crude plant extracts.     

Meso-四（对烷氧苯基）卟啉金属镁配合物的激光解吸电离飞行时间质谱表征

采用激光解吸电离飞行时间质谱法对meso-四（对烷氧苯基）卟啉金属镁配合物进行了表征。讨论了不同长度的烷基链对金属镁配合物激光质谱法结果的影响,并测定了它们的准确分子质量。分析结果表明,激光解吸电离飞行时间质谱是表征系列meso-四（对烷氧苯基）卟啉金属镁配合物的有效方法。     

Identification and characterization of molecular targets of natural products by mass spectrometry

Natural products, and their derivatives and mimics, have contributed to the development of important therapeutics to combat diseases such as infections and cancers over the past decades. The value of natural products to modern drug discovery is still considerable. However, its development is hampered by a lack of a mechanistic understanding of their molecular action, as opposed to the emerging molecule‐targeted therapeutics that are tailored to a specific protein target(s). Recent advances in the mass spectrometry‐based proteomic approaches have the potential to offer unprecedented insights into the molecular action of natural products. Chemical proteomics is established as an invaluable tool for the identification of protein targets of natural products. Small‐molecule affinity selection combined with mass spectrometry is a successful strategy to “fish” cellular targets from the entire proteome. Mass spectrometry‐based profiling of protein expression is also routinely employed to elucidate molecular pathways involved in the therapeutic and possible toxicological responses upon treatment with natural products. In addition, mass spectrometry is increasingly utilized to probe structural aspects of natural products–protein interactions. Limited proteolysis, photoaffinity labeling, and hydrogen/deuterium exchange in conjunction with mass spectrometry are sensitive and high‐throughput strategies that provide low‐resolution structural information of non‐covalent natural product–protein complexes. In this review, we provide an overview on the applications of mass spectrometry‐based techniques in the identification and characterization of natural product–protein interactions, and we describe how these applications might revolutionize natural product‐based drug discovery. © 2009 Wiley Periodicals, Inc., Mass Spec Rev 29:126–155, 2010     

电喷雾多级串联质谱快速鉴定木鳖子皂苷

利用电喷雾正负离子多级串联质谱相结合的方法 ,并结合皂苷部分醇解产物和皂苷元的质谱数据 ,鉴定了木鳖子皂苷的结构 ,推断了木鳖子皂苷的电喷雾质谱机理     

ESI-MS法研究白芍炮制前后化学成分的变化

ESI-MS analytical method was employed to study extracts of unprocessed and processed Radix Paeoniae alba. The results of the experiments prove that different processed methods is making a certain different influence on the contents of chemical components in Radix Paeoniae alba. This method is simple and accurate. It can be used for analyse of Traditional Chinese Medicine(TCM).     

质谱在新药研究中应用的回顾

回顾了质谱在新药研究中的一些应用 ,包括新药合成、化学结构确证、质量控制以及药物代谢物的鉴定等。综述了基质辅助激光解吸电离 \飞行时间质谱 ( Matrix-assistant laser desorption ionization time-of-flight mass spectrometry,MALDI/ TOFMS)、电喷雾电离质谱 ( Electrode spray ionization m ass spectrome-try,ESI-MS)等仪器及其联用技术在生物大分子药物研究 ,包括蛋白质组学、肽图谱、氨基酸序列、核苷酸分析等方面的进展 ,展望了质谱在未来生命科学中广阔的应用前景。     

吴茱萸生物碱的串联质谱分析

The fragmentation behavior of five alkaloids isolated from Fructus Evodiae by ion trap electrospray ionization tandem mass spectrometry (ESI-MSⁿ) is investigated. Major and diagnostic fragment ions were identified and their origins are proposed. Their fragmentation patterns and products were useful for their characterization. Known or unknown alkaloids could be analyzed in the crude extracts of Fructus Evodiae using the summarized fragmentation rules.     

Mass spectrometric characterization of high-valent metal-oxo, -peroxo and -peroxy intermediates of relevance in oxidation processes

The coupling of mass spectrometry with ionization techniques like electrospray ionization (ESI) or matrix-assisted matrix-assisted laser desorption-ionization (MALDI) offers many advantages over other well-established spectroscopic techniques employed for the investigation of intermediates or short-lived species in condensed-phase. In this review we describe some of the applications of mass spectrometry, in particular of ESI-MS to the detection and characterization of high-valent metal-oxo, -peroxo and -peroxy derivatives, crucial intermediates in the oxyfunctionalization of organic substrates. In addition, by utilizing gas-phase ion-molecule reactions and MS/MS experiments, information on the intrinsic reactivity of the short-lived intermediates may be obtained. The combined use of ESI-MS in association with other spectroscopic techniques and theoretical calculations is discussed as well.     

基于纳米毛细管的非变性质谱分析

非变性质谱利用电喷雾电离质谱技术从非变性缓冲溶液中研究自然折叠状态下的蛋白质、核酸及其复合物,是大型蛋白质组装体、蛋白质-药物复合物、核酸-配体复合物的结构、组成及其相互作用解析的重要工具。生化缓冲溶液中的非挥发性盐能提供足够的离子强度和适宜的pH值,以维持蛋白质、核酸分子折叠和结合状态,但通常与电喷雾电离质谱不兼容。基于纳米毛细管的电喷雾电离具备强大的基质耐受能力,为直接从生理或近生理缓冲溶液中完成蛋白质及其复合物的高效离子化提供了可能,极大地促进了近年来非变性质谱的应用研究。本文综述了纳米毛细管的制备与表征方法及其尺寸和界面性质导致的电离行为特性,回顾了近10年来纳米毛细管在非变性质谱中的应用研究进展。