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Chemical Reviews Apr 2022Solution-phase hydrogen/deuterium exchange (HDX) coupled to mass spectrometry (MS) is a widespread tool for structural analysis across academia and the biopharmaceutical... (Review)
Review
Solution-phase hydrogen/deuterium exchange (HDX) coupled to mass spectrometry (MS) is a widespread tool for structural analysis across academia and the biopharmaceutical industry. By monitoring the exchangeability of backbone amide protons, HDX-MS can reveal information about higher-order structure and dynamics throughout a protein, can track protein folding pathways, map interaction sites, and assess conformational states of protein samples. The combination of the versatility of the hydrogen/deuterium exchange reaction with the sensitivity of mass spectrometry has enabled the study of extremely challenging protein systems, some of which cannot be suitably studied using other techniques. Improvements over the past three decades have continually increased throughput, robustness, and expanded the limits of what is feasible for HDX-MS investigations. To provide an overview for researchers seeking to utilize and derive the most from HDX-MS for protein structural analysis, we summarize the fundamental principles, basic methodology, strengths and weaknesses, and the established applications of HDX-MS while highlighting new developments and applications.
Topics: Deuterium; Deuterium Exchange Measurement; Hydrogen; Hydrogen Deuterium Exchange-Mass Spectrometry; Mass Spectrometry; Proteins
PubMed: 34493042
DOI: 10.1021/acs.chemrev.1c00279 -
International Journal of Molecular... Apr 2016Mass spectrometry-based metabolome profiling became the method of choice in systems biology approaches and aims to enhance biological understanding of complex biological... (Review)
Review
Mass spectrometry-based metabolome profiling became the method of choice in systems biology approaches and aims to enhance biological understanding of complex biological systems. Genomics, transcriptomics, and proteomics are well established technologies and are commonly used by many scientists. In comparison, metabolomics is an emerging field and has not reached such high-throughput, routine and coverage than other omics technologies. Nevertheless, substantial improvements were achieved during the last years. Integrated data derived from multi-omics approaches will provide a deeper understanding of entire biological systems. Metabolome profiling is mainly hampered by its diversity, variation of metabolite concentration by several orders of magnitude and biological data interpretation. Thus, multiple approaches are required to cover most of the metabolites. No software tool is capable of comprehensively translating all the data into a biologically meaningful context yet. In this review, we discuss the advantages of metabolome profiling and main obstacles limiting progress in systems biology.
Topics: Chromatography, High Pressure Liquid; Databases, Factual; Gas Chromatography-Mass Spectrometry; Magnetic Resonance Spectroscopy; Mass Spectrometry; Metabolome; Metabolomics; Systems Biology
PubMed: 27128910
DOI: 10.3390/ijms17050632 -
Acta Pharmacologica Sinica Dec 2022Natural products (NPs) and their structural analogs represent a major source of novel drug development for disease prevention and treatment. The development of new drugs... (Review)
Review
Natural products (NPs) and their structural analogs represent a major source of novel drug development for disease prevention and treatment. The development of new drugs from NPs includes two crucial aspects. One is the discovery of NPs from medicinal plants/microorganisms, and the other is the evaluation of the NPs in vivo at various physiological and pathological states. The heterogeneous spatial distribution of NPs in medicinal plants/microorganisms or in vivo can provide valuable information for drug development. However, few molecular imaging technologies can detect thousands of compounds simultaneously on a label-free basis. Over the last two decades, mass spectrometry imaging (MSI) methods have progressively improved and diversified, thereby allowing for the development of various applications of NPs in plants/microorganisms and in vivo NP research. Because MSI allows for the spatial mapping of the production and distribution of numerous molecules in situ without labeling, it provides a visualization tool for NP research. Therefore, we have focused this mini-review on summarizing the applications of MSI technology in discovering NPs from medicinal plants and evaluating NPs in preclinical studies from the perspective of new drug research and development (R&D). Additionally, we briefly reviewed the factors that should be carefully considered to obtain the desired MSI results. Finally, the future development of MSI in new drug R&D is proposed.
Topics: Biological Products; Mass Spectrometry; Plants; Research; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 36229602
DOI: 10.1038/s41401-022-00990-8 -
The Analyst Feb 2019Direct sampling mass spectrometry (MS) has been advancing aggressively, showing immense potential in translating MS into the clinical field. Unlike traditional MS... (Review)
Review
Direct sampling mass spectrometry (MS) has been advancing aggressively, showing immense potential in translating MS into the clinical field. Unlike traditional MS analysis involving extensive sample preparation and chromatographic separation, quick and simple procedures with minimal sample pretreatment or purification became available with direct sampling. An overview of the development in this field is provided, including some representative ambient ionization and fast extraction methods. Quantitative applications of these methods are emphasized and their efficacy are highlighted from a clinical aspect; non-quantitative applications in clinical analysis are also discussed. This review also discusses the integration of direct sampling MS with miniature mass spectrometers and its future outlook as an emerging clinical tool for point-of-care analysis.
Topics: Humans; Mass Spectrometry; Point-of-Care Systems; Specimen Handling
PubMed: 30520890
DOI: 10.1039/c8an01722k -
Trends in Pharmacological Sciences Sep 2022Mass spectrometry imaging (MSI) is a powerful technique that combines the ability of microscopy to provide spatial information about multiple molecular species with the... (Review)
Review
Mass spectrometry imaging (MSI) is a powerful technique that combines the ability of microscopy to provide spatial information about multiple molecular species with the specificity of mass spectrometry (MS) for unlabeled mapping of analytes in diverse biological tissues. Initial pharmacological applications focused on drug distributions in different organs, including the compartmentalized brain. However, recent technological advances in instrumentation, software, and chemical tools have allowed its use in quantitative spatial omics. It now enables visualization of distributions of diverse molecules at high lateral resolution in studies of the pharmacokinetic and neuropharmacodynamic effects of drugs on functional biomolecules. Therefore, it has become a versatile technique with a multitude of applications that have transformed neuropharmacological research and enabled research into brain physiology at unprecedented resolution, as described in this review.
Topics: Humans; Mass Spectrometry; Neuropharmacology
PubMed: 35803758
DOI: 10.1016/j.tips.2022.06.005 -
Biochemical Society Transactions Jun 2022Structural Biology has moved beyond the aim of simply identifying the components of a cellular subsystem towards analysing the dynamics and interactions of multiple... (Review)
Review
Structural Biology has moved beyond the aim of simply identifying the components of a cellular subsystem towards analysing the dynamics and interactions of multiple players within a cell. This focal shift comes with additional requirements for the analytical tools used to investigate these systems of increased size and complexity, such as Native Mass Spectrometry, which has always been an important tool for structural biology. Scientific advance and recent developments, such as new ways to mimic a cell membrane for a membrane protein, have caused established methods to struggle to keep up with the increased demands. In this review, we summarize the possibilities, which Laser Induced Liquid Bead Ion Desorption (LILBID) mass spectrometry offers with regard to the challenges of modern structural biology, like increasingly complex sample composition, novel membrane mimics and advanced structural analysis, including next neighbor relations and the dynamics of complex formation.
Topics: Ions; Lasers; Mass Spectrometry; Membrane Proteins; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 35695670
DOI: 10.1042/BST20190881 -
Mass Spectrometry Reviews 2024Exploring the chemical content of individual cells not only reveals underlying cell-to-cell chemical heterogeneity but is also a key component in understanding how cells... (Review)
Review
Exploring the chemical content of individual cells not only reveals underlying cell-to-cell chemical heterogeneity but is also a key component in understanding how cells combine to form emergent properties of cellular networks and tissues. Recent technological advances in many analytical techniques including mass spectrometry (MS) have improved instrumental limits of detection and laser/ion probe dimensions, allowing the analysis of micron and submicron sized areas. In the case of MS, these improvements combined with MS's broad analyte detection capabilities have enabled the rise of single-cell and single-organelle chemical characterization. As the chemical coverage and throughput of single-cell measurements increase, more advanced statistical and data analysis methods have aided in data visualization and interpretation. This review focuses on secondary ion MS and matrix-assisted laser desorption/ionization MS approaches for single-cell and single-organelle characterization, which is followed by advances in mass spectral data visualization and analysis.
Topics: Single-Cell Analysis; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Humans; Animals; Organelles; Spectrometry, Mass, Secondary Ion; Mass Spectrometry
PubMed: 37010120
DOI: 10.1002/mas.21841 -
Mass Spectrometry Reviews Jan 2022Membrane proteins are incredibly important biomolecules because they mediate interactions between a cell's external and internal environment. Obtaining information about... (Review)
Review
Membrane proteins are incredibly important biomolecules because they mediate interactions between a cell's external and internal environment. Obtaining information about membrane protein structure and interactions is thus important for understanding these essential biomolecules. Compared with the analyses of water-soluble proteins, the structural analysis of membrane proteins is more challenging owing to their unique chemical properties and the presence of lipid components that are necessary to solubilize them. The combination of covalent labeling (CL) and mass spectrometry (MS) has recently been applied with great success to study membrane protein structure and interactions. These studies have demonstrated the many advantages that CL-MS methods have over other traditional biophysical techniques. In this review, we discuss both amino acid-specific and non-specific labeling approaches and the special considerations needed to address the unique challenges associated with interrogating membrane proteins. This review highlights the aspects of this approach that require special care to be applied correctly and provides a comprehensive review of the membrane protein systems that have been studied by CL-MS. © 2020 John Wiley & Sons Ltd. Mass Spec Rev.
Topics: Amino Acids; Mass Spectrometry; Membrane Proteins
PubMed: 33145813
DOI: 10.1002/mas.21667 -
Mass Spectrometry Reviews Jan 2022Laser ionization mass spectrometry (LIMS) was one of the first practical methods developed for in situ analysis of the surfaces of solid samples. This review will... (Review)
Review
Laser ionization mass spectrometry (LIMS) was one of the first practical methods developed for in situ analysis of the surfaces of solid samples. This review will encompass several aspects related to this analytical method. First, we will discuss the process of laser ionization, the influence of the laser type on its performance, and imaging capabilities of this method. In the second chapter, we will follow the historic development of LIMS instrumentation. After a brief overview of the first-generation instruments developed in 1960-1990 years, we will discuss in detail more recent designs, which appeared during the last 2-3 decades. In the last part of our review, we will cover the recent applications of LIMS for surface analysis. These applications include various types of analyses of solid inorganic, organic, and heterogeneous samples, often in combination with depth profiling and imaging capability.
Topics: Lasers; Mass Spectrometry; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 33169900
DOI: 10.1002/mas.21669 -
Expert Review of Proteomics Aug 2014Mass spectrometry-based plasma proteomics is a field where intense research has been performed during the last decade. Being closely linked to biomarker discovery, the... (Review)
Review
Mass spectrometry-based plasma proteomics is a field where intense research has been performed during the last decade. Being closely linked to biomarker discovery, the field has received a fair amount of criticism, mostly due to the low number of novel biomarkers reaching the clinic. However, plasma proteomics is under gradual development with improvements on fractionation methods, mass spectrometry instrumentation and analytical approaches. These recent developments have contributed to the revival of plasma proteomics. The goal of this review is to summarize these advances, focusing in particular on fractionation methods, both for targeted and global mass spectrometry-based plasma analysis.
Topics: Animals; Chromatography, Liquid; Glycoproteins; Humans; Mass Spectrometry; Plasma; Proteome
PubMed: 24661227
DOI: 10.1586/14789450.2014.901157