Analysis of carbohydrates and glycoconjugates by matrix-assisted laser desorption/ionization mass spectrometry: An update for 2017–2018

This review is the tenth update of the original article published in 1999 on the application of matrix-assisted laser desorption/ionization mass spectrometry (MALDI) mass spectrometry to the analysis of carbohydrates and glycoconjugates and brings coverage of the literature to the end of 2018. Also included are papers that describe methods appropriate to glycan and glycoprotein analysis by MALDI, such as sample preparation techniques, even though the ionization method is not MALDI. Topics covered in the first part of the review include general aspects such as theory of the MALDI process, new methods, matrices, derivatization, MALDI imaging, fragmentation and the use of arrays. The second part of the review is devoted to applications to various structural types such as oligo- and poly-saccharides, glycoproteins, glycolipids, glycosides, and biopharmaceuticals. Most of the applications are presented in tabular form. The third part of the review covers medical and industrial applications of the technique, studies of enzyme reactions, and applications to chemical synthesis. The reported work shows increasing use of combined new techniques such as ion mobility and highlights the impact that MALDI imaging is having across a range of diciplines. MALDI is still an ideal technique for carbohydrate analysis and advancements in the technique and the range of applications continue steady progress.     

衍生化技术在MALDI质谱成像中的应用进展

近年来，基质辅助激光解吸离子化（matrix-assisted laser desorption ionization, MALDI）质谱成像（mass spectrometry imaging, MSI）技术发展迅速，在很多领域均有广泛应用。质谱成像技术虽然可以同时得到上百个化合物的数据，但是对于低丰度、离子化效率低和易受基质峰干扰的化合物的成像分析仍然极具挑战。为了提高质谱成像中目标分子的信号响应，将原位衍生化方法应用于质谱成像技术中是非常必要的。衍生化方法与质谱成像的结合已成功实现了不同类型目标分析物的成像分析，且均展现了优异的效果。本文综述了样本上原位衍生化方法在MALDI质谱成像中的应用，包括用于含有羧基、氨基、醛基等活性基团的目标分子的衍生化试剂和衍生化反应，以及衍生化的基质选择和试剂的涂覆装置，并展望了衍生化方法结合MALDI质谱成像技术的发展趋势。     

利用质谱技术解析糖类结构的研究进展

糖类物质是重要的生物信息分子,在许多生命活动中发挥着重要作用。糖类物质的结构非常复杂,其结构解析一直是糖生物学研究的瓶颈。在糖类物质结构解析的诸多方法中,质谱技术被认为是一种不可缺少的重要手段。本工作综述了质谱及色谱-质谱联用法在糖类结构解析中的研究进展,包括电子轰击质谱、化学电离质谱、快原子轰击质谱、电喷雾质谱、基质辅助激光解析电离质谱、色谱-质谱联用技术(气相色谱-质谱和液相色谱-质谱),并比较了各种方法在糖类物质定性、定量分析中的优缺点。随着质谱技术的不断发展,糖链的释放和衍生化方法的不断改进,以及谱图解析工作的进一步深入,质谱技术必将成为糖类物质结构解析的有力工具。     

Analysis of carbohydrates and glycoconjugates by matrix-assisted laser desorption/ionization mass spectrometry: an update for 2007-2008

This review is the fifth update of the original review, published in 1999, on the application of MALDI mass spectrometry to the analysis of carbohydrates and glycoconjugates and brings coverage of the literature to the end of 2008. The first section of the review covers fundamental studies, fragmentation of carbohydrate ions, use of derivatives and new software developments for analysis of carbohydrate spectra. Among newer areas of method development are glycan arrays, MALDI imaging and the use of ion mobility spectrometry. The second section of the review discusses applications of MALDI MS to the analysis of different types of carbohydrate. Specific compound classes that are covered include carbohydrate polymers from plants, N- and O-linked glycans from glycoproteins, biopharmaceuticals, glycated proteins, glycolipids, glycosides and various other natural products. There is a short section on the use of MALDI mass spectrometry for the study of enzymes involved in glycan processing and a section on the use of MALDI MS to monitor products of the chemical synthesis of carbohydrates with emphasis on carbohydrate-protein complexes and glycodendrimers. Corresponding analyses by electrospray ionization now appear to outnumber those performed by MALDI and the amount of literature makes a comprehensive review on this technique impractical. However, most of the work relating to sample preparation and glycan synthesis is equally relevant to electrospray and, consequently, those proposing analyses by electrospray should also find material in this review of interest.     

On-tissue chemical derivatization in mass spectrometry imaging

Mass spectrometry imaging (MSI) combines molecular and spatial information in a valuable tool for a wide range of applications. Matrix-assisted laser desorption/ionization (MALDI) is at the forefront of MSI ionization due to its wide availability and increasing improvement in spatial resolution and analysis speed. However, ionization suppression, low concentrations, and endogenous and methodological interferences cause visualization problems for certain molecules. Chemical derivatization (CD) has proven a viable solution to these issues when applied in mass spectrometry platforms. Chemical tagging of target analytes with larger, precharged moieties aids ionization efficiency and removes analytes from areas of potential isobaric interferences. Here, we address the application of CD on tissue samples for MSI analysis, termed on-tissue chemical derivatization (OTCD). MALDI MSI will remain the focus platform due to its popularity, however, alternative ionization techniques such as liquid extraction surface analysis and desorption electrospray ionization will also be recognized. OTCD reagent selection, application, and optimization methods will be discussed in detail. MSI with OTCD is a powerful tool to study the spatial distribution of poorly ionizable molecules within tissues. Most importantly, the use of OTCD−MSI facilitates the analysis of previously inaccessible biologically relevant molecules through the adaptation of existing CD methods. Though further experimental optimization steps are necessary, the benefits of this technique are extensive.     

基于离子淌度质谱技术的离子光谱研究进展

离子光谱结合了质谱的高灵敏度和光谱的分子结构特异性的优势,可对蛋白质、多肽、糖类、寡核苷酸等复杂体系进行结构表征和鉴定。但当存在同分异构体时,离子光谱难以从叠加的谱图中得到单个异构体的光谱信息。离子淌度质谱技术可通过区分待测离子质荷比和分子空间尺寸差异来实现异构体的分离。离子淌度可以对异构体分离后分别引入到后续的光谱和质谱分析中,减少了由异构体引起的光谱叠加问题,光谱可以进一步验证离子淌度的分离效果,因此质谱、光谱、离子淌度谱的有机结合在得到异构体精确光谱的同时,也为离子淌度质谱分析带来了新的维度和深度。本文概述了近20年来基于各类离子淌度质谱技术的光谱仪器发展和应用情况,总结目前存在的问题,并展望多维度结构质谱的新需求。     

Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for the period 2005–2006

This review is the fourth update of the original review, published in 1999, on the application of MALDI mass spectrometry to the analysis of carbohydrates and glycoconjugates and brings coverage of the literature to the end of 2006. The review covers fundamental studies, fragmentation of carbohydrate ions, method developments, and applications of the technique to the analysis of different types of carbohydrate. Specific compound classes that are covered include carbohydrate polymers from plants, N‐ and O‐linked glycans from glycoproteins, glycated proteins, glycolipids from bacteria, glycosides, and various other natural products. There is a short section on the use of MALDI‐TOF mass spectrometry for the study of enzymes involved in glycan processing, a section on industrial processes, particularly the development of biopharmaceuticals and a section on the use of MALDI–MS to monitor products of chemical synthesis of carbohydrates. Large carbohydrate–protein complexes and glycodendrimers are highlighted in this final section. © 2010 Wiley Periodicals, Inc., Mass Spec Rev 30:1–100, 2011     

Analysis of carbohydrates and glycoconjugates by matrix-assisted laser desorption/ionization mass spectrometry: An update covering the period 1999-2000

This review describes the use of matrix-assisted laser desorption/ionization (MALDI) mass spectrometry for the analysis of carbohydrates and glycoconjugates and continues coverage of the field from the previous review published in 1999 (D. J. Harvey, Matrix-assisted laser desorption/ionization mass spectrometry of carbohydrates, 1999, Mass Spectrom Rev, 18:349-451) for the period 1999-2000. As MALDI mass spectrometry is acquiring the status of a mature technique in this field, there has been a greater emphasis on applications rather than to method development as opposed to the previous review. The present review covers applications to plant-derived carbohydrates, N- and O-linked glycans from glycoproteins, glycated proteins, mucins, glycosaminoglycans, bacterial glycolipids, glycosphingolipids, glycoglycerolipids and related compounds, and glycosides. Applications of MALDI mass spectrometry to the study of enzymes acting on carbohydrates (glycosyltransferases and glycosidases) and to the synthesis of carbohydrates, are also covered.     

Mass spectrometric analysis of long-chain lipids

Electrospray and matrix assisted laser desorption ionization generate abundant molecular ion species from all known lipids that have long chain fatty acyl groups esterified or amidated to many different polar headgroup features. Molecular ion species include both positive ions from proton addition [M+H](+) and negative ions from proton abstraction [M-H](-) as well as positive ions from alkali metal attachment and negative ions from acetate or chloride attachment. Collisional activation of both MALDI and ESI behave very similarly in that generated molecular species yield product ions that reveal many structural features of the fatty acyl lipids that can be detected in tandem mass spectrometric experiments. For many lipid species, collision induced dissociation of the positive [M+H](+) reveals information about the polar headgroup, while collision induced dissociation of the negative [M-H](-) provides information about the fatty acyl chain. The mechanisms of formation of many of these lipid product ions have been studied in detail and many established pathways are reviewed here. Specific examples of mass spectrometric behavior of several molecular species are presented, including fatty acids, triacylglycerol, phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, phosphatidylglycerol, ceramide, and sphingomeylin.     

ReactionSequenceofMatrix-AssistedLaserDesorption/Ionization

The reaction sequence of matrix-assisted laser desorption/ionization (MALDI) was examined using various analytical techniques, including mass spectrometry and optical spectroscopy. Photoelectron emission was found to be occurred with laser fluences much less than the threshold fluence for ion production. Photoionization is the most probable initial ionization reaction in MALDI, and the photoelectrons are mainly produced from crystalline matrix because the ionization potential of matrix molecules reduced considerably in large matrix clusters. Ab initio calculations predicted that the photoionization can be achieved by using two photons of commonly used laser wavelengths. For 2,5-dihydroxybenzoic acid (DHB) and sinapinic acid (SA), the threshold fluences for photoelectron emission are unable to increase the surface temperature for material desorption. Negative ions may be produced via electron-capture ionization of matrix molecules when the laser fluence is high enough to promote material desorption. Proton and electron disproportionations may contribute to the ion production when the laser fluences further increase. Because the abundances of photoelectrons in the ion source region with laser fluences for ion production of various matrices are different, individual matrix molecule may develop a unique reaction pathway. Based on the results, a qualitative reaction sequence of MALDI is discussed.     

槲皮素的电喷雾离子阱质谱分析

应用电喷雾离子阱正负离子扫描技术对槲皮素的结构和质谱裂解规律进行比较研究,并采用Mass Frontier 3.0软件辅助解析正离子扫描条件下槲皮素的主要特征碎片离子及其裂解规律。槲皮素正离子扫描的ESI MS裂解特征是出现碎片 m/z 287、285、275、267、257及229,碎片m/z 285和275可继续裂解成碎片 m/z 257、229。碎片 m/z 283、273、257、245和229的形成及碎片 m/z 283、273裂解成碎片 m/z 255是槲皮素负离子扫描的ESI-MS裂解特征。槲皮素的正负离子扫描质谱裂解规律基本相似,但负离子提供的碎片信息较少。本研究为进一步探求该化合物的体内代谢转化,结构优化和修饰提供了有价值的依据。     

Analysis of carbohydrates and glycoconjugates by matrix-assisted laser desorption/ionization mass spectrometry: An update for 2003-2004

This review is the third update of the original review, published in 1999, on the application of matrix-assisted laser desorption/ionization (MALDI) mass spectrometry to the analysis of carbohydrates and glycoconjugates and brings the topic to the end of 2004. Both fundamental studies and applications are covered. The main topics include methodological developments, matrices, fragmentation of carbohydrates and applications to large polymeric carbohydrates from plants, glycans from glycoproteins and those from various glycolipids. Other topics include the use of MALDI MS to study enzymes related to carbohydrate biosynthesis and degradation, its use in industrial processes, particularly biopharmaceuticals and its use to monitor products of chemical synthesis where glycodendrimers and carbohydrate-protein complexes are highlighted.     

核苷5'-硫代磷酰氨基酸酯的电喷雾质谱研究

核苷磷酰氨基酸酯化合物是一类倍受重视的药物,特别是它可作为寡聚核苷酸的类似物用于反义药物[1]。核苷逆转录酶抑制剂被批准用于治疗爱滋病（AIDS）,目前普遍使用的抗HIV核苷类似物中,2',3'-双脱氧核苷（ddNs）具有良好的疗效[2],它的抗病毒的可能机理是在细胞激酶的作用下,5'-羟基发生相继的磷酸化,生成三磷酸核苷,然后通过HIV-逆转录酶进入病毒DNA的合成,由于ddNs 3'-没有相应的羟基存在,使得病毒DNA的合成得以终止。McGuigan C.等学者报道苯氧基取代的核苷-磷酰氨基酸酯是HIV逆转录酶的有效抑制剂,同时与ddNs相比…     

Imaging mass spectrometry

Imaging mass spectrometry combines the chemical specificity and parallel detection of mass spectrometry with microscopic imaging capabilities. The ability to simultaneously obtain images from all analytes detected, from atomic to macromolecular ions, allows the analyst to probe the chemical organization of a sample and to correlate this with physical features. The sensitivity of the ionization step, sample preparation, the spatial resolution, and the speed of the technique are all important parameters that affect the type of information obtained. Recently, significant progress has been made in each of these steps for both secondary ion mass spectrometry (SIMS) and matrix-assisted laser desorption/ionization (MALDI) imaging of biological samples. Examples demonstrating localization of proteins in tumors, a reduction of lamellar phospholipids in the region binding two single celled organisms, and sub-cellular distributions of several biomolecules have all contributed to an increasing upsurge in interest in imaging mass spectrometry. Here we review many of the instrumental developments and methodological approaches responsible for this increased interest, compare and contrast the information provided by SIMS and MALDI imaging, and discuss future possibilities.     

A tutorial in small molecule identification via electrospray ionization‐mass spectrometry: The practical art of structural elucidation

The identification of unknown molecules has been one of the cornerstone applications of mass spectrometry for decades. This tutorial reviews the basics of the interpretation of electrospray ionization‐based MS and MS/MS spectra in order to identify small‐molecule analytes (typically below 2000 Da). Most of what is discussed in this tutorial also applies to other atmospheric pressure ionization methods like atmospheric pressure chemical/photoionization. We focus primarily on the fundamental steps of MS‐based structural elucidation of individual unknown compounds, rather than describing strategies for large‐scale identification in complex samples. We critically discuss topics like the detection of protonated and deprotonated ions ([M + H]⁺ and [M ? H]^?) as well as other adduct ions, the determination of the molecular formula, and provide some basic rules on the interpretation of product ion spectra. Our tutorial focuses primarily on the fundamental steps of MS‐based structural elucidation of individual unknown compounds (eg, contaminants in chemical production, pharmacological alteration of drugs), rather than describing strategies for large‐scale identification in complex samples. This tutorial also discusses strategies to obtain useful orthogonal information (UV/Vis, H/D exchange, chemical derivatization, etc) and offers an overview of the different informatics tools and approaches that can be used for structural elucidation of small molecules. It is primarily intended for beginning mass spectrometrists and researchers from other mass spectrometry sub‐disciplines that want to get acquainted with structural elucidation are interested in some practical tips and tricks.

     

Electron ionization time-of-flight mass spectrometry: historical review and current applications

This review presents an overview of electron ionization time-of-flight mass spectroscopy (EITOFMS), beginning with its early development to the employment of modern high-resolution electron ionization sources. The EITOFMS is demonstrated to be ideally suited for analytical and basic chemical physics studies. Studies of the formation of positive ions by electron ionization time-of-flight mass spectroscopy have been responsible for many of the known ionization potentials of molecules and radicals, as well as accepted bond dissociation energies for ions and neutral molecules. The application of TOFMS has been particularly important in the area of negative ion physics and chemistry. A wide variety of negative ion properties have been discovered and studied by using these methods including: autodetachment lifetimes, metastable dissociation, Rydberg electron transfer reactions and field detachment, SF(6) Scavenger method for detecting temporary negative ion states, and many others.     

Electrospray mass spectrometry of phospholipids

Phospholipids play a central role in the biochemistry of all living cells. These molecules constitute the lipid bilayer defining the outer confines of a cell, but also serve as the structural entities which confine subcellular components. Mass spectrometry has emerged as a powerful tool useful for the qualitative and quantitative analysis of complex phospholipids, including glycerophospholipids and the sphingolipid, sphingomyelin. Collision induced decomposition of both positive and negative molecular ion species yield rich information as to the polar head group of the phospholipid and the fatty-acyl substituents esterified to the glycerophospholipid backbone. This review presents the current level of understanding of the mechanisms involved in the formation of various product ions following collisional activation of molecular ion species generated by electrospray ionization of the common glycerophospholipids, including phosphatidic acid, phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol, phosphatidylglycerol, phosphatidylserine, cardiolipin, and sphingomyelin. Recent advances in the application of matrix assisted laser desorption ionization is also considered. Several applications of mass spectrometry applied to phospholipid analysis are presented as they apply to physiology as well as pathophysiology.     

直接输注电喷雾电离四极杆飞行时间质谱在十六种中药来源化合物定性分析中的应用(英文)

采用直接输注电喷雾电离质谱对十六种中药来源的化合物进行了分析。观察了它们的电喷雾电离质谱和串联质谱特征 ,以了解不同结构化合物的电离能力和裂解特点。观察表明 :为使样品成分尽可能多地被检测 ,必须同时进行正负两种模式的分析。化合物结构中羰基的存在似有利于化合物在正离子模式下形成准分子离子或其它分子加和离子。当采样锥电压为 3 0 V时 ,大多数化合物能形成准分子离子或其它分子加和离子。但改变采样锥电压似不能完全避免源内裂解。建议分析时同时考察不同采样锥电压 (如 1 0 V、3 0 V和 5 0 V)。串联质谱分析被证明是获得进一步结构信息的有效手段 ,因为对于所有被观察的准分子离子和其它分子加和离子 ,均能在串联质谱分析中检测到碎片离子。本研究在四物汤的研究中已经成功地运用了该方法。此方法有助于中药混合物中样品成分的快速定性分析