Showing papers in "Mass Spectrometry Reviews in 2016"
TL;DR: Recent applications of metabolomics are described and its increasing application to study plant responses to environmental (stress-) factors, including drought, salt, low oxygen caused by waterlogging or flooding of the soil, temperature, light and oxidative stress are described.
Abstract: Metabolomics is one omics approach that can be used to acquire comprehensive information on the composition of a metabolite pool to provide a functional screen of the cellular state. Studies of the plant metabolome include analysis of a wide range of chemical species with diverse physical properties, from ionic inorganic compounds to biochemically derived hydrophilic carbohydrates, organic and amino acids, and a range of hydrophobic lipid-related compounds. This complexitiy brings huge challenges to the analytical technologies employed in current plant metabolomics programs, and powerful analytical tools are required for the separation and characterization of this extremely high compound diversity present in biological sample matrices. The use of mass spectrometry (MS)-based analytical platforms to profile stress-responsive metabolites that allow some plants to adapt to adverse environmental conditions is fundamental in current plant biotechnology research programs for the understanding and development of stress-tolerant plants. In this review, we describe recent applications of metabolomics and emphasize its increasing application to study plant responses to environmental (stress-) factors, including drought, salt, low oxygen caused by waterlogging or flooding of the soil, temperature, light and oxidative stress (or a combination of them). Advances in understanding the global changes occurring in plant metabolism under specific abiotic stress conditions are fundamental to enhance plant fitness and increase stress tolerance. © 2015 Wiley Periodicals, Inc. Mass Spec Rev 35:620-649, 2016.
243 citations
TL;DR: An overall view of all instrumental and methodological developments for DBS analysis with mass spectrometric detection, with and without separation techniques is presented.
Abstract: Dried blood spots (DBS) typically consist in the deposition of small volumes of capillary blood onto dedicated paper cards. Comparatively to whole blood or plasma samples, their benefits rely in the fact that sample collection is easier and that logistic aspects related to sample storage and shipment can be relatively limited, respectively, without the need of a refrigerator or dry ice. Originally, this approach has been developed in the sixties to support the analysis of phenylalanine for the detection of phenylketonuria in newborns using bacterial inhibition test. In the nineties tandem mass spectrometry was established as the detection technique for phenylalanine and tyrosine. DBS became rapidly recognized for their clinical value: they were widely implemented in pediatric settings with mass spectrometric detection, and were closely associated to the debut of newborn screening (NBS) programs, as a part of public health policies. Since then, sample collection on paper cards has been explored with various analytical techniques in other areas more or less successfully regarding large-scale applications. Moreover, in the last 5 years a regain of interest for DBS was observed and originated from the bioanalytical community to support drug development (e.g., PK studies) or therapeutic drug monitoring mainly. Those recent applications were essentially driven by improved sensitivity of triple quadrupole mass spectrometers. This review presents an overall view of all instrumental and methodological developments for DBS analysis with mass spectrometric detection, with and without separation techniques. A general introduction to DBS will describe their advantages and historical aspects of their emergence. A second section will focus on blood collection, with a strong emphasis on specific parameters that can impact quantitative analysis, including chromatographic effects, hematocrit effects, blood effects, and analyte stability. A third part of the review is dedicated to sample preparation and will consider off-line and on-line extractions; in particular, instrumental designs that have been developed so far for DBS extraction will be detailed. Flow injection analysis and applications will be discussed in section IV. The application of surface analysis mass spectrometry (DESI, paper spray, DART, APTDCI, MALDI, LDTD-APCI, and ICP) to DBS is described in section V, while applications based on separation techniques (e.g., liquid or gas chromatography) are presented in section VI. To conclude this review, the current status of DBS analysis is summarized, and future perspectives are provided.
201 citations
TL;DR: This review describes the recent applications of HILIC-MS/MS in metabolomic studies, ranging from amino acids, lipids, nucleotides, organic acids, pharmaceuticals, and metabolites of specific nature, as well as tissues from animals and humans.
Abstract: Hydrophilic interaction chromatography (HILIC) is an emerging separation mode of liquid chromatography (LC). Using highly hydrophilic stationary phases capable of retaining polar/ionic metabolites, and accompany with high organic content mobile phase that offer readily compatibility with mass spectrometry (MS) has made HILIC an attractive complementary tool to the widely used reverse-phase (RP) chromatographic separations in metabolomic studies. The combination of HILIC and RPLC coupled with an MS detector expands the number of detected analytes and provides more comprehensive metabolite coverage than use of only RP chromatography. This review describes the recent applications of HILIC-MS/MS in metabolomic studies, ranging from amino acids, lipids, nucleotides, organic acids, pharmaceuticals, and metabolites of specific nature. The biological systems investigated include microbials, cultured cell line, plants, herbal medicine, urine, and serum as well as tissues from animals and humans. Owing to its unique capability to measure more-polar biomolecules, the HILIC separation technique would no doubt enhance the comprehensiveness of metabolite detection, and add significant value for metabolomic investigations. © 2014 Wiley Periodicals, Inc. Mass Spec Rev 35:574-600, 2016.
179 citations
TL;DR: In this review, the invention of the ion trap with dynamic harmonization which demonstrated the highest resolving power ever achieved is summarized.
Abstract: Fourier transform ion cyclotron resonance (FT ICR) mass spectrometer offers highest resolving power and mass accuracy among all types of mass spectrometers. Its unique analytical characteristics made FT ICR important tool for proteomics, metabolomics, petroleomics, and investigation of complex mixtures. Signal acquisition in FT ICR MS takes long time (up to minutes). During this time ion-ion interaction considerably affects ion motion and result in decreasing of the resolving power. Understanding of those effects required complicated theory and supercomputer simulations but culminated in the invention of the ion trap with dynamic harmonization which demonstrated the highest resolving power ever achieved. In this review we summarize latest achievements in theory and simulation of FT ICR mass spectrometers.
152 citations
TL;DR: In this review, the main imaging mass spectrometry techniques are discussed, as well as the nature of biological samples and molecules, which might be analyzed by such methodology.
Abstract: Imaging Mass Spectrometry (IMS) is strengthening its position as a valuable analytical tool. It has unique ability to identify structures and to unravel molecular changes that occur in the precisely defined part of the sample. These unique features open new possibilities in the field of various aspects of biological research. In this review we briefly discuss the main imaging mass spectrometry techniques, as well as the nature of biological samples and molecules, which might be analyzed by such methodology. Moreover, a novel approach, where different analytical techniques might be combined with the results of IMS study, is emphasized and discussed. With such a fast development of IMS and related methods, we can foresee the promising future of this technique. © 2015 Wiley Periodicals, Inc. Mass Spec Rev 35: 147–169, 2016.
146 citations
TL;DR: This review of differential mobility spectrometry focuses primarily on mass spectrometer coupling, starting with the history of the development of this technique in the Soviet Union.
Abstract: This review of differential mobility spectrometry focuses primarily on mass spectrometry coupling, starting with the history of the development of this technique in the Soviet Union. Fundamental principles of the separation process are covered, in addition to efforts related to design optimization and advancements in computer simulations. The flexibility of differential mobility spectrometry design features is explored in detail, particularly with regards to separation capability, speed, and ion transmission. 2015 Wiley Periodicals, Inc. Mass Spec Rev 35:687-737, 2016.
145 citations
TL;DR: There has been a recent surge in the development of mass spectrometric methods for detailed characterization of naphthenic acid fraction compounds (all C(c)H(h)N(n)O(o)S), species, species, including heteroatomic and aromatic components in the acid-extractable fraction) in environmental samples.
Abstract: There has been a recent surge in the development of mass spectrometric methods for detailed characterization of naphthenic acid fraction compounds (all C(c)H(h)N(n)O(o)S(s), species, including heteroatomic and aromatic components in the acid-extractable fraction) in environmental samples. This surge is driven by the increased activity in oil sands environmental monitoring programs in Canada, the exponential increase in research studies on the isolation and toxicity identification of components in oil sands process water (OSPW), and the analytical requirements for development of technologies for treatment of OSPW. There has been additional impetus due to the parallel studies to control corrosion from naphthenic acids during the mining and refining of heavy bitumen and crude oils. As a result, a range of new mass spectrometry tools have been introduced since our last major review of this topic in 2009. Of particular significance are the developments of combined mass spectrometric methods that incorporate technologies such as gas chromatography, liquid chromatography, and ion mobility. There has been additional progress with respect to improved visualization methods for petroleomics and oil sands environmental forensics. For comprehensive coverage and more reliable characterization of samples, an approach based on multiple-methods that employ two or more ionization modes is recommended. On-line or off-line fractionation of isolated extracts, with or without derivatization, might also be used prior to mass spectrometric analyses. Individual ionization methods have their associated strengths and weaknesses, including biases, and thus dependence upon a single ionization method is potentially misleading. There is also a growing trend to not rely solely on low-resolution mass spectrometric methods (<20,000 resolving power at m/z 200) for characterization of complex samples. Future research is anticipated to focus upon (i) structural elucidation of components to determine the correlation with toxicity or corrosion, (ii) verification of characterization studies based on authentic reference standards and reference materials, and (iii) integrated approaches based on multiple-methods and ionization methods for more-reliable oil sands environmental forensics.
139 citations
TL;DR: This paper will cover the combination of novel MS machines [single quadrupole (Q) and triple quadrupoles, isotope ratio, low- and high-resolution time-of-flight (ToF), hybrid (Q-ToF)] to GC’s systems, and will position comprehensive two-dimensional gas chromatography within the wider context of separation science.
Abstract: The present contribution is focused on the evolution and current trends of comprehensive two-dimensional gas chromatography-mass spectrometry (GC × GC-MS), with respect to a review that described this specific methodology published at the beginning of 2008 (Mondello et al., 2008). In fact, since then there has been considerable evolution in the MS field, certainly exceeding that observed in GC × GC. In particular, the present paper will cover the combination of novel MS machines [single quadrupole (Q) and triple quadrupole, isotope ratio, low- and high-resolution time-of-flight (ToF), hybrid (Q-ToF)] to GC × GC systems, and will position comprehensive two-dimensional gas chromatography within the wider context of separation science. © 2014 Wiley Periodicals, Inc. Mass Spec Rev 35:524-534, 2016.
109 citations
TL;DR: The new challenge for the future will be reducing the false positive rate by using second-tier tests, avoiding false negative results by using new specific biomarkers and introducing new treatable disorders in NBS programs.
Abstract: Tandem mass spectrometry (MS/MS) has become a leading technology used in clinical chemistry and has shown to be particularly sensitive and specific when used in newborn screening (NBS) tests. The success of tandem mass spectrometry is due to important advances in hardware, software and clinical applications during the last 25 years. MS/MS permits a very rapid measurement of many metabolites in different biological specimens by using filter paper spots or directly on biological fluids. Its use in NBS give us the chance to identify possible treatable metabolic disorders even when asymptomatic and the benefits gained by this type of screening is now recognized worldwide. Today the use of MS/MS for second-tier tests and confirmatory testing is promising especially in the early detection of new disorders such as some lysosomal storage disorders, ADA and PNP SCIDs, X-adrenoleucodistrophy (X-ALD), Wilson disease, guanidinoacetate methyltransferase deficiency (GAMT), and Duchenne muscular dystrophy. The new challenge for the future will be reducing the false positive rate by using second-tier tests, avoiding false negative results by using new specific biomarkers and introducing new treatable disorders in NBS programs.
90 citations
TL;DR: An overview of this fast-growing field to help orient MS-based research on extracellular vesicles and the role of alternative analytical approaches, like gel-based proteomics and antibody-based immunoassays, are mentioned.
Abstract: The review briefly summaries main features of extracellular vesicles, a joint terminology for exosomes, microvesicles, and apoptotic vesicles. These vesicles are in the center of interest in biology and medical sciences, and form a very active field of research. Mass spectrometry (MS), with its specificity and sensitivity, has the potential to identify and characterize molecular composition of these vesicles; but as yet there are only a limited, but fast-growing, number of publications that use MS workflows in this field. MS is the major tool to assess protein composition of extracellular vesicles: qualitative and quantitative proteomics approaches are both reviewed. Beside proteins, lipid and metabolite composition of vesicles might also be best assessed by MS techniques; however there are few applications as yet in this respect. The role of alternative analytical approaches, like gel-based proteomics and antibody-based immunoassays, are also mentioned. The objective of the review is to give an overview of this fast-growing field to help orient MS-based research on extracellular vesicles. © 2015 Wiley Periodicals, Inc. Mass Spec Rev 35: 3–21, 2016.
88 citations
TL;DR: Plasma-based ambient ionization mass spectrometry techniques are gaining growing interest due to their specific features, such as the need for little or no sample preparation, its high analysis speed, and the ambient experimental conditions.
Abstract: Plasma-based ambient ionization mass spectrometry techniques are gaining growing interest due to their specific features, such as the need for little or no sample preparation, its high analysis speed, and the ambient experimental conditions. Samples can be analyzed in gas, liquid, or solid forms. These techniques allow for a wide range of applications, like warfare agent detection, chemical reaction control, mass spectrometry imaging, polymer identification, and food safety monitoring, as well as applications in biomedical science, e.g., drug and pharmaceutical analysis, medical diagnostics, biochemical analysis, etc. Until now, the main drawback of plasma-based techniques is their quantitative aspect, but a lot of efforts have been done to improve this obstacle. © 2015 Wiley Periodicals, Inc. Mass Spec Rev 35: 22–34, 2016.
TL;DR: Both approaches are capable of studying non-covalently bound biomolecules even in quite challenging systems, such as membrane protein complexes.
Abstract: Non-covalent interactions are essential for the structural organization of biomacromolecules and play an important role in molecular recognition processes, such as the interactions between proteins, glycans, lipids, DNA, and RNA. Mass spectrometry (MS) is a powerful tool for studying of non-covalent interactions, due to the low sample consumption, high sensitivity, and label-free nature. Nowadays, native-ESI MS is heavily used in studies of non-covalent interactions and to understand the architecture of biomolecular complexes. However, MALDI-MS is also becoming increasingly useful. It is challenging to detect the intact complex without fragmentation when analyzing non-covalent interactions with MALDI-MS. There are two methodological approaches to do so. In the first approach, different experimental and instrumental parameters are fine-tuned in order to find conditions under which the complex is stable, such as applying non-acidic matrices and collecting first-shot spectra. In the second approach, the interacting species are "artificially" stabilized by chemical crosslinking. Both approaches are capable of studying non-covalently bound biomolecules even in quite challenging systems, such as membrane protein complexes. Herein, we review and compare native-ESI and MALDI MS for the study of non-covalent interactions.
TL;DR: Data indicate that charge-state distribution (CSD) analysis can provide valuable structural information on normally folded, as well as disordered structures in ESI-MS experiments.
Abstract: Electrospray-ionization mass spectrometry (ESI-MS) is a key tool of structural biology, complementing the information delivered by conventional biochemical and biophysical methods. Yet, the mechanism behind the conformational effects in protein ESI-MS is an object of debate. Two parameters—solvent-accessible surface area (As) and apparent gas-phase basicity (GBapp)—are thought to play a role in controlling the extent of protein ionization during ESI-MS experiments. This review focuses on recent experimental and theoretical investigations concerning the influence of these parameters on ESI-MS results and the structural information that can be derived. The available evidence supports a unified model for the ionization mechanism of folded and unfolded proteins. These data indicate that charge-state distribution (CSD) analysis can provide valuable structural information on normally folded, as well as disordered structures. © 2015 Wiley Periodicals, Inc. Rapid Commun Mass Spectrom 9999: XX–XX, 2015.
TL;DR: A review of the existing applications of ion soft- and reactive landing and the physical phenomena that occur during and after ion soft landing, including retention and reduction of ionic charge along with factors that impact the efficiency of ion deposition.
Abstract: Soft- and reactive landing of mass-selected ions is gaining attention as a promising approach for the precisely-controlled preparation of materials on surfaces that are not amenable to deposition using conventional methods. A broad range of ionization sources and mass filters are available that make ion soft-landing a versatile tool for surface modification using beams of hyperthermal (<100 eV) ions. The ability to select the mass-to-charge ratio of the ion, its kinetic energy and charge state, along with precise control of the size, shape, and position of the ion beam on the deposition target distinguishes ion soft landing from other surface modification techniques. Soft- and reactive landing have been used to prepare interfaces for practical applications as well as precisely-defined model surfaces for fundamental investigations in chemistry, physics, and materials science. For instance, soft- and reactive landing have been applied to study the surface chemistry of ions isolated in the gas-phase, prepare arrays of proteins for high-throughput biological screening, produce novel carbon-based and polymer materials, enrich the secondary structure of peptides and the chirality of organic molecules, immobilize electrochemically-active proteins and organometallics on electrodes, create thin films of complex molecules, and immobilize catalytically active organometallics as well as ligated metal clusters. In addition, soft landing has enabled investigation of the size-dependent behavior of bare metal clusters in the critical subnanometer size regime where chemical and physical properties do not scale predictably with size. The morphology, aggregation, and immobilization of larger bare metal nanoparticles, which are directly relevant to the design of catalysts as well as improved memory and electronic devices, have also been studied using ion soft landing. This review article begins in section 1 with a brief introduction to the existing applications of ion soft- and reactive landing. Section 2 provides an overview of the ionization sources and mass filters that have been used to date for soft landing of mass-selected ions. A discussion of the competing processes that occur during ion deposition as well as the types of ions and surfaces that have been investigated follows in section 3. Section 4 discusses the physical phenomena that occur during and after ion soft landing, including retention and reduction of ionic charge along with factors that impact the efficiency of ion deposition. The influence of soft landing on the secondary structure and biological activity of complex ions is addressed in section 5. Lastly, an overview of the structure and mobility as well as the catalytic, optical, magnetic, and redox properties of bare ionic clusters and nanoparticles deposited onto surfaces is presented in section 6. © 2015 Wiley Periodicals, Inc. Mass Spec Rev. 00:1–41, 2015
TL;DR: This review will discuss the newly developed hyphenation strategies for CE-ESI-MS and their application in bottom-up proteomics as well as the applications in the same time span, 2009 to present, using co-axial sheathliquid.
Abstract: With the development of more sensitive hyphenation strategies for capillary electrophoresis-electrospray-mass spectrometry the technique has reemerged as technique with high separation power combined with high sensitivity in the analysis of peptides and protein digests This review will discuss the newly developed hyphenation strategies for CE-ESI-MS and their application in bottom-up proteomics as well as the applications in the same time span, 2009 to present, using co-axial sheathliquid Subsequently all separate aspects in the development of a CE-ESI-MS method for bottom-up proteomics shall be discussed, highlighting certain applications and discussing pros and cons of the various choices The separation of peptides in a capillary electrophoresis system is discussed including the great potential for modeling of this migration of peptides due to the simple electrophoretic separation process Furthermore, the technical aspects of method development are discussed, namely; background electrolyte choice, coating of the separation capillary and chosen loading method Finally, conclusions and an outlook on future developments in the field of bottom-up proteomics by CE-ESI-MS will be provided
TL;DR: The enrichment approaches used in siderophore analysis and current ICP-MS technologies are reviewed, and the recent tools for fast dereplication of secondary metabolites and their databases are reported.
Abstract: Siderophores play important roles in microbial iron piracy, and are applied as infectious disease biomarkers and novel pharmaceutical drugs. Inductively coupled plasma and molecular mass spectrometry (ICP-MS) combined with high resolution separations allow characterization of siderophores in complex samples taking advantages of mass defect data filtering, tandem mass spectrometry, and iron-containing compound quantitation. The enrichment approaches used in siderophore analysis and current ICP-MS technologies are reviewed. The recent tools for fast dereplication of secondary metabolites and their databases are reported. This review on siderophores is concluded with their recent medical, biochemical, geochemical, and agricultural applications in mass spectrometry context.
TL;DR: This review covers the literature of the past decade devoted to the tandem mass spectrometric investigation of nucleic acids, with the main focus on the fundamental mechanistic aspects governing the gas-phase dissociation of DNA, RNA, modified oligonucleotide analogues, and their adducts with metal ions.
Abstract: Nucleic acids play key roles in the storage and processing of genetic information, as well as in the regulation of cellular processes. Consequently, they represent attractive targets for drugs against gene-related diseases. On the other hand, synthetic oligonucleotide analogues have found application as chemotherapeutic agents targeting cellular DNA and RNA. The development of effective nucleic acid-based chemotherapeutic strategies requires adequate analytical techniques capable of providing detailed information about the nucleotide sequences, the presence of structural modifications, the formation of higher-order structures, as well as the interaction of nucleic acids with other cellular components and chemotherapeutic agents. Due to the impressive technical and methodological developments of the past years, tandem mass spectrometry has evolved to one of the most powerful tools supporting research related to nucleic acids. This review covers the literature of the past decade devoted to the tandem mass spectrometric investigation of nucleic acids, with the main focus on the fundamental mechanistic aspects governing the gas-phase dissociation of DNA, RNA, modified oligonucleotide analogues, and their adducts with metal ions. Additionally, recent findings on the elucidation of nucleic acid higher-order structures by tandem mass spectrometry are reviewed. © 2014 Wiley Periodicals, Inc., Mass Spec Rev 35:483-523, 2016.
TL;DR: A deeper understanding of the MALDI-ISD process is necessary to fully exploit this method, which favors the production of fragmentation pathways involving "hydrogen-abundant" and "Hydrogen-deficient" radical precursors, respectively.
Abstract: Matrix-assisted laser desorption/ionization in-source decay (MALDI-ISD) is a very easy way to obtain large sequence tags and, thereby, reliable identification of peptides and proteins Recently discovered new matrices have enhanced the MALDI-ISD yield and opened new research avenues The use of reducing and oxidizing matrices for MALDI-ISD of peptides and proteins favors the production of fragmentation pathways involving "hydrogen-abundant" and "hydrogen-deficient" radical precursors, respectively Since an oxidizing matrix provides information on peptide/protein sequences complementary to that obtained with a reducing matrix, MALDI-ISD employing both reducing and oxidizing matrices is a potentially useful strategy for de novo peptide sequencing Moreover, a pseudo-MS(3) method provides sequence information about N- and C-terminus extremities in proteins and allows N- and C-terminal side fragments to be discriminated within the complex MALDI-ISD mass spectrum The combination of high mass resolution of a Fourier transform-ion cyclotron resonance (FTICR) analyzer and the software suitable for MALDI-ISD facilitates the interpretation of MALDI-ISD mass spectra A deeper understanding of the MALDI-ISD process is necessary to fully exploit this method Thus, this review focuses first on the mechanisms underlying MALDI-ISD processes, followed by a discussion of MALDI-ISD applications in the field of proteomics © 2014 Wiley Periodicals, Inc, Mass Spec Rev 35:535-556, 2016
TL;DR: A proof of knowledge-based critical review aims at exploring the selected applications of those defined omics technologies in the hepatocellular carcinoma (HCC) niche with an emphasis on translational applications driven by advanced mass spectrometry, toward the specific clinical use for HCC patients.
Abstract: Hepatocellular carcinoma (HCC) is one of the primary hepatic malignancies and is the third most common cause of cancer related death worldwide. Although a wealth of knowledge has been gained concerning the initiation and progression of HCC over the last half century, efforts to improve our understanding of its pathogenesis at a molecular level are still greatly needed, to enable clinicians to enhance the standards of the current diagnosis and treatment of HCC. In the post-genome era, advanced mass spectrometry driven multi-omics technologies (e.g., profiling of DNA damage adducts, RNA modification profiling, proteomics, and metabolomics) stand at the interface between chemistry and biology, and have yielded valuable outcomes from the study of a diversity of complicated diseases. Particularly, these technologies are being broadly used to dissect various biological aspects of HCC with the purpose of biomarker discovery, interrogating pathogenesis as well as for therapeutic discovery. This proof of knowledge-based critical review aims at exploring the selected applications of those defined omics technologies in the HCC niche with an emphasis on translational applications driven by advanced mass spectrometry, toward the specific clinical use for HCC patients. This approach will enable the biomedical community, through both basic research and the clinical sciences, to enhance the applicability of mass spectrometry-based omics technologies in dissecting the pathogenesis of HCC and could lead to novel therapeutic discoveries for HCC.
TL;DR: Time-of-flight mass spectrometry is reviewed from its inception in the 1940s to the present day and of ion sources to the extent that sources influence analyzers.
Abstract: Time-of-flight mass spectrometry is reviewed from its inception in the 1940s to the present day. The review is concerned with fundamentals of time-of-flight analyzers and of ion sources to the extent that sources influence analyzers. The patent literature has been covered, and efforts made to bring to light less well-known papers and studies © 2015 Wiley Periodicals, Inc. Mass Spec Rev. 35:738-757, 2016.
TL;DR: These phosphoproteomic applications with ICP-MS as elemental detector are reviewed and the advantage of the parallel use of molecular and elemental mass spectrometry is stressed.
Abstract: The authors acknowledge the Flemish Institute for Technological Research (VITO). Evelyne Maes is funded by a Stichting Emmanuel van der Schueren research grant of the Vlaamse Liga tegen Kanker (VLK).
TL;DR: The recent developments in the use of mass spectrometry, together with general and widely used affinity enrichment approaches, for the proteome-wide capture, identification and quantification of nucleotide-binding proteins, including protein kinases, ATPases, GTPases, and other nucleotide -binding proteins are reviewed.
Abstract: Nucleotide-binding proteins, such as protein kinases, ATPases and GTP-binding proteins, are among the most important families of proteins that are involved in a number of pivotal cellular processes. However, global study of the structure, function, and expression level of nucleotide-binding proteins as well as protein-nucleotide interactions can hardly be achieved with the use of conventional approaches owing to enormous diversity of the nucleotide-binding protein family. Recent advances in mass spectrometry (MS) instrumentation, coupled with a variety of nucleotide-binding protein enrichment methods, rendered MS-based proteomics a powerful tool for the comprehensive characterizations of the nucleotide-binding proteome, especially the kinome. Here, we review the recent developments in the use of mass spectrometry, together with general and widely used affinity enrichment approaches, for the proteome-wide capture, identification and quantification of nucleotide-binding proteins, including protein kinases, ATPases, GTPases, and other nucleotide-binding proteins. The working principles, advantages, and limitations of each enrichment platform in identifying nucleotide-binding proteins as well as profiling protein-nucleotide interactions are summarized. The perspectives in developing novel MS-based nucleotide-binding protein detection platform are also discussed. © 2014 Wiley Periodicals, Inc. Mass Spec Rev 35:601-619, 2016.
TL;DR: This review will discuss the developments at the intersection of mass spectrometry-based proteomics and protein structure determination and start from a brief overview of the classic approaches to identify protein structure along with their advantages and disadvantages.
Abstract: Typically, mass spectrometry is used to identify the peptides present in a complex peptide mixture and subsequently the precursor proteins. As such, mass spectrometry focuses mainly on the primary structure, the (modified) amino acid sequence of peptides and proteins. In contrast, the three-dimensional structure of a protein is typically determined with protein X-ray crystallography or NMR. Despite the close relationship between these two aspects of protein studies (sequence and structure), mass spectrometry and structure determination are not frequently combined. Nevertheless, this combination of approaches, dubbed conformational proteomics, can offer insight into the function, working mechanism, and conformational status of a protein. In this review, we will discuss the developments at the intersection of mass spectrometry-based proteomics and protein structure determination and start from a brief overview of the classic approaches to identify protein structure along with their advantages and disadvantages. We will subsequently discuss the ability of mass spectrometry to overcome some of the hurdles of these classic methods. Finally, we will provide an outlook on the interplay of mass spectrometry and protein structure determination, and highlight several recent experiments in which mass spectrometry was successfully used to either aid or complement structure elucidation. © 2014 Wiley Periodicals, Inc. Mass Spec Rev 35:653-665, 2016.
TL;DR: This review briefly summarizes the different analytical approaches to detect and separate anions and focuses on the recently introduced PIESI method to present the most effective dicationic, tricationsic, and tetracationic reagents for the detection of singly and multiply charged anion and some zwitterions.
Abstract: The negative-ion mode of electrospray ionization mass spectrometry (ESI-MS) is intrinsically less sensitive than the positive-ion mode. The detection and quantitation of anions can be performed in positive-ion mode by forming specific ion-pairs during the electrospray process. The paired-ion electrospray ionization (PIESI) method uses specially synthesized multifunctional cations to form positively charged adducts with the anions to be analyzed. The adducts are detected in the positive-ion mode and at higher m/z ratios to produce excellent signal-to-noise ratios and limits of detection that often are orders of magnitude better than those obtained with native anions in the negative-ion mode. This review briefly summarizes the different analytical approaches to detect and separate anions. It focuses on the recently introduced PIESI method to present the most effective dicationic, tricationic, and tetracationic reagents for the detection of singly and multiply charged anions and some zwitterions. The mechanism by which specific structural molecular architectures can have profound effects on signal intensities is also addressed.
TL;DR: This review is focused on ESI-MS studies of copper-catalyzed reactions, and the plethora of mass spectrometric approaches demonstrated is demonstrated on copper mediated C-H activations, cross coupling reactions, rearrangements, organocuprate chemistry, and other examples.
Abstract: Electrospray ionization mass spectrometry (ESI-MS) is becoming an important tool for mechanistic studies in organic and organometallic chemistry. It allows investigation of reaction mixtures including monitoring of reactants, products, and intermediates, studying properties of the intermediates and their reactivity. Studying the reactive species in the gas phase can be advantageously combined with theoretical calculations. This review is focused on ESI-MS studies of copper-catalyzed reactions. Possible effects of the electrospray process on the transfer of the copper complexes to the gas phase are discussed. The plethora of mass spectrometric approaches is demonstrated on copper mediated C-H activations, cross coupling reactions, rearrangements, organocuprate chemistry, and other examples. © 2015 Wiley Periodicals, Inc. Mass Spec Rev 35: 85–110, 2016.
TL;DR: The function of different trace elements in liver health and disease is summarized and the present knowledge on how quantitative biometal imaging techniques such as synchrotron X-ray fluorescence microscopy, secondary ion mass spectrometry, and laser ablation inductively coupled plasma mass Spectrometry enrich diagnostics in the detection and quantification of hepatic metal disorders is discussed.
Abstract: The liver is the most central organ and the largest gland of the body that influences and controls a variety of metabolic and catabolic processes. It produces inconceivable many essential proteins, is responsible for the recovery of various food components, degrades toxins, mediates the bile production, and is involved in the excretion of unwanted metabolites. Several of these anabolic or catabolic functions of the liver depend on trace elements. These are either integral part of enzymes, cofactors, or act as chemical catalysts. Therefore, a lack of trace elements can lead to organ failure or systemic illness. Conversely, excessive hepatic trace element deposition resulting from genetic disorders, intoxication, extensive dietary supply, or long-term parenteral nutrition may cause hepatic inflammation, fibrosis, cirrhosis, and even hepatocellular carcinoma. Although specific serum parameters currently allow rough assessment of metal deficit and excess, the precise quantification of hepatic metal content in liver is presently only possible by different titration or staining techniques of biopsy specimens. Recently, novel innovative metal imaging techniques were developed that are on the way to replace these traditional methods. In the present review, we summarize the function of different trace elements in liver health and disease and discuss the present knowledge on how quantitative biometal imaging techniques such as synchrotron X-ray fluorescence microscopy, secondary ion mass spectrometry, and laser ablation inductively coupled plasma mass spectrometry enrich diagnostics in the detection and quantification of hepatic metal disorders. We will further discuss sample preparation, sensitivity, spatial resolution, specificity, quantification strategies, and potential future applications of metal bioimaging in experimental research and clinical daily routine. © 2015 Wiley Periodicals, Inc. Mass Spec Rev 35:666-686, 2016.
TL;DR: The aim of this review is to critically analyze recent literature on charged supramolecular assemblies formed by surfactant molecules in gas phase to focus on the most important achievements gained in recent years by molecular dynamics simulations and mass spectrometry techniques.
Abstract: The aim of this review is to critically analyze recent literature on charged supramolecular assemblies formed by surfactant molecules in gas phase. Apart our specific interest on this research area, the stimuli to undertake the task arise from the widespread theoretical and applicative benefits emerging from a comprehensive view of this topic. In fact, the study of the formation, stability, and physicochemical peculiarities of non-covalent assemblies of surfactant molecules in gas phase allows to unveil interesting aspects such as the role of attractive, repulsive, and steric intermolecular interactions as driving force of supramolecular organization in absence of interactions with surrounding medium and the size and charge state dependence of aggregate structural and dynamical properties. Other interesting aspects worth to be investigated are joined to the ability of these assemblies to incorporate selected solubilizates molecules as well as to give rise to chemical reactions within a single organized structure. In particular, the incorporation of large molecules such as proteins has been of recent interest with the objective to protect their structure and functionality during the transition from solution to gas phase. Exciting fall-out of the study of gas phase surfactant aggregates includes mass and energy transport in the atmosphere, origin of life and simulation of supramolecular aggregation in the interstellar space. Moreover, supramolecular assemblies of amphiphilic molecules in gas phase could find remarkable applications as atmospheric cleaning agents, nanosolvents and nanoreactors for specialized chemical processes in confined space. Mass spectrometry techniques have proven to be particularly suitable to generate these assemblies and to furnish useful information on their size, size polydispersity, stability, and structural organization. On the other hand molecular dynamics simulations have been very useful to rationalize many experimental findings and to furnish a vivid picture of the structural and dynamic features of these aggregates. Thus, in this review, we will focus on the most important achievements gained in recent years by both these investigative tools. © 2015 Wiley Periodicals, Inc. Mass Spec Rev 35: 170–187, 2016.
TL;DR: The application of modern MS techniques for the assessment of polymer degradation products, frequently bearing characteristic end groups that can be revealed and differentiated by MS, will be discussed within the context of specific degradation pathways.
Abstract: Contemporary reports by Polish authors on the application of mass spectrometric methods for the elucidation of the subtle molecular structure of biodegradable polymers and their degradation products will be presented. Special emphasis will be given to natural aliphatic (co)polyesters (PHA) and their synthetic analogues, formed through anionic ring-opening polymerization (ROP) of β-substituted β-lactones. Moreover, the application of MS techniques for the evaluation of the structure of biodegradable polymers obtained in ionic and coordination polymerization of cyclic ethers and esters as well as products of step-growth polymerization, in which bifunctional or multifunctional monomers react to form oligomers and eventually long chain polymers, will be discussed. Furthermore, the application of modern MS techniques for the assessment of polymer degradation products, frequently bearing characteristic end groups that can be revealed and differentiated by MS, will be discussed within the context of specific degradation pathways. Finally, recent Polish accomplishments in the area of mass spectrometry will be outlined. © 2015 Wiley Periodicals, Inc. Rapid Commun. Mass Spectrom. 9999: XX–XX, 2015.
TL;DR: This review article describes the origins, advantages, and application of an indirect approach with which to study protein and other macromolecular complexes and identify the nature and site of interaction interfaces by means of conventional matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS).
Abstract: This review article describes the origins, advantages, and application of an indirect approach with which to study protein and other macromolecular complexes and identify the nature and site of interaction interfaces by means of conventional matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). First reported in 1999, it involves the detection of ion depletion or the absence of ions associated with a binding partner or domain in the MALDI mass spectrum of a mixture of interacting components compared to that for an untreated control. Later referred to as intensity-fading in some applications, the method offers numerous advantages over the direct detection of protein and other macromolecule complexes by MALDI-MS and even electrospray ionization (ESI) MS. The origins of this indirect method, its development for use with gel-separated components, validation using companion biochemical assays, and application to a range of protein-antibody and protein-drug complexes are reviewed together with software specifically developed to aid with data interpretation. The sensitivity of the approach for revealing how subtle differences in the structure of the binding partners can be detected by MALDI-MS is also demonstrated. © 2015 Wiley Periodicals, Inc. Mass Spec Rev 35:559-573, 2016.
TL;DR: The present review attempted to collect the results of both experimental and computational studies of the aforementioned reactions conducted since the very beginning of gas-phase negative ion chemistry.
Abstract: Reactions of aromatic and heteroaromatic compounds involving anions are of great importance in organic synthesis. Some of these reactions have been studied in the gas phase and are occasionally mentioned in reviews devoted to gas-phase negative ion chemistry, but no reviews exist that collect all existing information about these reactions. This work is intended to fill this gap. In the first part of this review, methods for generating arene anions in the gas phase and studying their physicochemical properties and fragmentation reactions are presented. The main topics in this part are as follows: processes in which gas-phase arene anions are formed, measurements and calculations of the proton affinities of arene anions, proton exchange reactions, and fragmentation processes of substituted arene anions, especially phenide ions. The second part is devoted to gas-phase reactions of arene anions. The most important of these are reactions with electrophiles such as carbonyl compounds and α,β-unsaturated carbonyl and related compounds (Michael acceptors). Other reactions including oxidation of arene anions and halogenophilic reactions are also presented. In the last part of the review, reactions of electrophilic arenes with nucleophiles are discussed. The best known of these is the aromatic nucleophilic substitution (SNAr) reaction; however, other processes that lead to the substitution of a hydrogen atom in the aromatic ring are also very important. Aromatic substrates in these reactions are usually but not always nitroarenes bearing other substituents in the ring. The first step in these reactions is the formation of an anionic σ-adduct, which, depending on the substituents in the aromatic ring and the structure of the attacking nucleophile, is either an intermediate or a transition state in the reaction path. In the present review, we attempted to collect the results of both experimental and computational studies of the aforementioned reactions conducted since the very beginning of gas-phase negative ion chemistry. © 2015 Wiley Periodicals, Inc. Mass Spec Rev.