Mass spectrometry analysis of the influenza virus

The role of mass spectrometry to probe characteristics of the influenza virus, and vaccine and antiviral drugs that target the virus, are reviewed. Genetic and proteomic approaches have been applied which incorporate high resolution mass spectrometry and mass mapping to genotype the virus and establish its evolution in terms of the primary structure of the surface protein antigens. A mass spectrometric immunoassay has been developed and applied to assess the structure and antigenicity of the virus in terms of the hemagglutinin antigen. The quantitation of the hemagglutinin antigen in vaccine preparations has also been conducted that is of importance to their efficacy. Finally, the characterization and quantitation of antiviral drugs against the virus, and their metabolites, have been monitored in blood, serum, and urine. The combined approaches demonstrate the strengths of modern mass spectrometric methods for the characterization of this killer virus. [This article was published online 10 September 2008. An error was subsequently identified. This notice is included in the online and print versions to indicate that both have been corrected 7 November 2008.]     

生物质谱技术及其在RNA检测中的应用

生命科学的需求促进质谱技术的发展,现代的质谱技术为生命科学研究提供丰富的检测手段,本文重点介绍生物质谱技术的特点、性能以及质谱技术的进展;及质谱技术在RNA研究领域的方法学,包括核酸的纯化方法、核酸的离子化技术、核酸的分子量检测技术和核酸质谱数据的解析方法及其软件;以及质谱在核酸领域的具体应用,包括质谱在测序、定量、转录后修饰、核酸的指纹识别、蛋白和核酸相互作用等方面的应用。     

Mass spectrometry in the proteome analysis of mature cereal kernels

In the last decade, the improved performance and versatility of the mass spectrometers together with the increasing availability of gene and genomic sequence database, led the mass spectrometry to become an indispensable tool for either protein and proteome analyses in cereals. Mass spectrometric works on prolamins have rapidly evolved from the determination of the molecular masses of proteins to the proteomic approaches aimed to a large‐scale protein identification and study of functional and regulatory aspects of proteins. Mass spectrometry coupled with electrophoresis, chromatographic methods, and bioinformatics tools is currently making significant contributions to a better knowledge of the composition and structure of the cereal proteins and their structure–function relationships. Results obtained using mass spectrometry, including characterization of prolamins, investigation of the gluten toxicity for coeliac patients, identification of proteins responsible of cereal allergies, determination of the protein pattern and its modification under environmental or stress effects, investigation of genetically modified varieties by proteomic approaches, are summarized here, to illustrate current trends, analytical troubles and challenges, and suggest possible future perspectives. © 2011 Wiley Periodicals, Inc. Mass Spec Rev 31:448–465, 2012     

Mass spectrometry analysis of nitrotyrosine‐containing proteins

Oxidative stress plays important roles in a wide range of diseases such as cancer, inflammatory disease, neurodegenerative disorders, etc. Tyrosine nitration in a protein is a chemically stable oxidative modification, and a marker of oxidative injuries. Mass spectrometry (MS) is a key technique to identify nitrotyrosine‐containing proteins and nitrotyrosine sites in endogenous and synthetic nitroproteins and nitropeptides. However, in vivo nitrotyrosine‐containing proteins occur with extreme low‐abundance to severely challenge the use of MS to identify in vivo nitroproteins and nitrotyrosine sites. A preferential enrichment of nitroproteins and/or nitropeptides is necessary before MS analysis. Current enrichment methods include immuno‐affinity techniques, chemical derivation of the nitro group plus target isolations, followed with tandem mass spectrometry analysis. This article reviews the MS techniques and pertinent before‐MS enrichment techniques for the identification of nitrotyrosine‐containing proteins. This article reviews future trends in the field of nitroproteomics, including quantitative nitroproteomics, systems biological networks of nitroproteins, and structural biology study of tyrosine nitration to completely clarify the biological functions of tyrosine nitration. © 2013 Wiley Periodicals, Inc. Mass Spec Rev 34: 423–448, 2015.     

Mass spectrometry in the quantitative analysis of therapeutic intracellular nucleotide analogs

Nucleoside analogs are widely used in anti‐cancer, anti‐(retro)viral, and immunosuppressive therapy. Nucleosides are prodrugs that require intracellular activation to mono‐, di‐, and finally triphosphates. Monitoring of these intracellular nucleotides is important to understand their pharmacology. The relatively involatile salts and ion‐pairing agents traditionally used for the separation of these ionic analytes limit the applicability of mass spectrometry (MS) for detection. Both indirect and direct methods have been developed to circumvent this apparent incompatibility. Indirect methods consist of de‐phosphorylation of the nucleotides into nucleosides before the actual analysis. Various direct approaches have been developed, ranging from the use of relatively volatile or very low levels of regular ion‐pairing agents, hydrophilic interaction chromatography (HILIC), weak anion‐exchange, or porous graphitic carbon columns to capillary electrophoresis and matrix‐assisted light desorption—time of flight (MALDI‐TOF) MS. In this review we present an overview of the publications describing the quantitative analysis of therapeutic intracellular nucleotide analogs using MS. The focus is on the different approaches for their direct analysis. We conclude that despite the technical hurdles, several useful MS‐compatible chromatographic approaches have been developed, enabling the use of the excellent selectivity and sensitivity of MS for the quantitative analysis of intracellular nucleotides. © 2010 Wiley Periodicals, Inc., Mass Spec Rev 30:321–343, 2011     

Mass spectrometry in ionospheric research

Mass spectrometry played a key role in the development of the understanding of the earth's ionosphere. Of primary importance was its use for in situ atmospheric measurements of the ion and neutral composition of the atmosphere. Mass spectrometry has also played an essential role in the laboratory measurement of critical ionospheric molecular processes. Examples of both are given.     

Mass spectrometry in aging research

This review covers the application of mass spectrometric techniques to aging research. Modern proteomic strategies will be discussed as well as the targeted analysis of specific proteins for the correlation of post-translational modifications with protein function. Selected examples will show both the power and also current limitations of the respective techniques. Experimental results and strategies are discussed in view of current theories of the aging process.     

Mass spectrometry in combinatorial chemistry

In the fast expanding field of combinatorial chemistry, profiling libraries has always been a matter of concern--as illustrated by the buoyant literature over the past seven years. Spectroscopic methods, including especially mass spectrometry and to a lesser extent IR and NMR, have been applied at different levels of combinatorial library synthesis: in the rehearsal phase to optimize the chemistry prior to library generation, to confirm library composition, and to characterize after screening each structure that exhibits positive response. Most of the efforts have been concentrated on library composition assessment. The difficulties of such analyses have evolved from the infancy of the combinatorial concept, where large mixtures were prepared, to the recent parallel syntheses of collections of discrete compounds. Whereas the complexity of the analyses has diminished, an increased degree of automation was simultaneously required to achieve efficient library component identification and quantification. In this respect, mass spectrometry has been found to be the method of choice, providing rapid, sensitive, and informative analyses, especially when coupled to chromatographic separation. Fully automated workstations able to cope with several hundreds of compounds per day have been designed. After a brief introduction to describe the combinatorial approach, library characterization will be discussed in detail, considering first the solution-based methodologies and secondly the support-bound material analyses.     

Mass spectrometry analysis of new chemical entities for pharmaceutical discovery

In this Section, we review the applications of mass spectrometry for the analysis and purification of new chemical entities (NCEs) for pharmaceutical discovery. Since the speed of synthesis of NCEs has dramatically increased over the last few years, new high throughput analytical techniques have been developed to keep pace with the synthetic developments. In this Section, we review both novel, as well as modifications of commonly used mass spectrometry techniques that have helped increase the speed of the analytical process. Part of the review is devoted to the purification of NCEs, which has undergone significant development in recent years, and the close integral association between characterization and purification to drive high throughput operations. At the end of the Section, we review potential future directions based on promising and exciting new developments.     

Mass spectrometry of oligosaccharides

Glycosylation is a common post-translational modification to cell surface and extracellular matrix (ECM) proteins as well as to lipids. As a result, cells carry a dense coat of carbohydrates on their surfaces that mediates a wide variety of cell-cell and cell-matrix interactions that are crucial to development and function. Because of the historical difficulties with the analysis of complex carbohydrate structures, a detailed understanding of their roles in biology has been slow to develop. Just as mass spectrometry has proven to be the core technology behind proteomics, it stands to play a similar role in the study of functional implications of carbohydrate expression, known as glycomics. This review summarizes the state of knowledge for the mass spectrometric analysis of oligosaccharides with regard to neutral, sialylated, and sulfated compound classes. Mass spectrometric techniques for the ionization and fragmentation of oligosaccharides are discussed so as to give the reader the background to make informed decisions to solve structure-activity relations in glycomics.     

Mass spectrometry in bioinorganic analytical chemistry

A considerable momentum has recently been gained by in vitro and in vivo studies of interactions of trace elements in biomolecules due to advances in inductively coupled plasma mass spectrometry (ICP MS) used as a detector in chromatography and capillary and planar electrophoresis. The multi-isotopic (including non-metals such as S, P, or Se) detection capability, high sensitivity, tolerance to matrix, and large linearity range regardless of the chemical environment of an analyte make ICP MS a valuable complementary technique to electrospray MS and MALDI MS. This review covers different facets of the recent progress in metal speciation in biochemistry, including probing in vitro interactions between metals and biomolecules, detection, determination, and structural characterization of heteroatom-containing molecules in biological tissues, and protein monitoring and quantification via a heteroelement (S, Se, or P) signal. The application areas include environmental chemistry, plant and animal biochemistry, nutrition, and medicine.     

Mass spectrometry imaging under ambient conditions

Mass spectrometry imaging (MSI) has emerged as an important tool in the last decade and it is beginning to show potential to provide new information in many fields owing to its unique ability to acquire molecularly specific images and to provide multiplexed information, without the need for labeling or staining. In MSI, the chemical identity of molecules present on a surface is investigated as a function of spatial distribution. In addition to now standard methods involving MSI in vacuum, recently developed ambient ionization techniques allow MSI to be performed under atmospheric pressure on untreated samples outside the mass spectrometer. Here we review recent developments and applications of MSI emphasizing the ambient ionization techniques of desorption electrospray ionization (DESI), laser ablation electrospray ionization (LAESI), probe electrospray ionization (PESI), desorption atmospheric pressure photoionization (DAPPI), femtosecond laser desorption ionization (fs‐LDI), laser electrospray mass spectrometry (LEMS), infrared laser ablation metastable‐induced chemical ionization (IR‐LAMICI), liquid microjunction surface sampling probe mass spectrometry (LMJ‐SSP MS), nanospray desorption electrospray ionization (nano‐DESI), and plasma sources such as the low temperature plasma (LTP) probe and laser ablation coupled to flowing atmospheric‐pressure afterglow (LA‐FAPA). Included are discussions of some of the features of ambient MSI for example the ability to implement chemical reactions with the goal of providing high abundance ions characteristic of specific compounds of interest and the use of tandem mass spectrometry to either map the distribution of targeted molecules with high specificity or to provide additional MS information on the structural identification of compounds. We also describe the role of bioinformatics in acquiring and interpreting the chemical and spatial information obtained through MSI, especially in biological applications for tissue diagnostic purposes. Finally, we discuss the challenges in ambient MSI and include perspectives on the future of the field. © 2012 Wiley Periodicals, Inc., Mass Spec Rev 32:218–243, 2013     

Mass spectrometry and the cellular surfaceome

The collection of exposed plasma membrane proteins, collectively termed the surfaceome, is involved in multiple vital cellular processes, such as the communication of cells with their surroundings and the regulation of transport across the lipid bilayer. The surfaceome also plays key roles in the immune system by recognizing and presenting antigens, with its possible malfunctioning linked to disease. Surface proteins have long been explored as potential cell markers, disease biomarkers, and therapeutic drug targets. Despite its importance, a detailed study of the surfaceome continues to pose major challenges for mass spectrometry-driven proteomics due to the inherent biophysical characteristics of surface proteins. Their inefficient extraction from hydrophobic membranes to an aqueous medium and their lower abundance compared to intracellular proteins hamper the analysis of surface proteins, which are therefore usually underrepresented in proteomic datasets. To tackle such problems, several innovative analytical methodologies have been developed. This review aims at providing an extensive overview of the different methods for surfaceome analysis, with respective considerations for downstream mass spectrometry-based proteomics.     

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