著者
Tohru Yamagaki Tsukiho Osawa
出版者
The Mass Spectrometry Society of Japan
雑誌
Mass Spectrometry (ISSN:2187137X)
巻号頁・発行日
vol.11, no.1, pp.A0109, 2022-12-28 (Released:2022-12-28)
参考文献数
12

The alkaloids epinastine, 3-methylxanthine and camptothecin were analyzed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). The ionization efficiencies of epinastine and 3-methylxanthine were improved upon the addition of 1,5-diaminoanthraquinone (DAAQ). DAAQ did not show ultraviolet absorbance peaks at wavelengths around 337 nm and 355 nm that are used in conventional MALDI-MS instruments. In addition, the DAAQ ion peak was very weak relative to those of the analytes due to the low absorbance efficiency. These properties of DAAQ are advantageous for the DAAQ-MALDI-MS analysis of alkaloids.
著者
Nanako Azegami Rina Taguchi Noa Suzuki Yusuke Sakata Tsuyoshi Konuma Satoko Akashi
出版者
The Mass Spectrometry Society of Japan
雑誌
Mass Spectrometry (ISSN:2187137X)
巻号頁・発行日
vol.11, no.1, pp.A0110, 2022-12-28 (Released:2022-12-28)
参考文献数
35

The contribution of disordered regions to protein function and structure is a relatively new field of study and of particular significance as their function has been implicated in some human diseases. Our objective was to analyze various deletion mutants of the bromodomain-containing protein 4 (BRD4) using native mass spectrometry to characterize the gas-phase behavior of the disordered region connected to the folded domain. A protein with a single bromodomain but no long disordered linker displayed a narrow charge distribution at low charge states, suggesting a compact structure. In contrast, proteins containing one or two bromodomains connected to a long disordered region exhibited multimodal charge distributions, suggesting the presence of compact and elongated conformers. In the presence of a pan-BET-bromodomain inhibitor, JQ1, the protein–JQ1 complex ions had relatively small numbers of positive charges, corresponding to compact conformers. In contrast, the ions with extremely high charge states did not form a complex with JQ1. This suggests that all of the JQ1-bound BRD4 proteins in the gas phase are in a compact conformation, including the linker region, while the unbound forms are considerably elongated. Although these are gas-phase phenomena, it is possible that the long disordered linker connected to the bromodomain causes the denaturation of the folded domain, which, in turn, affects its JQ1 recognition.
著者
Chihiro Ota Toshinobu Hondo Yumi Miyake Hiroshi Furutani Michisato Toyoda
出版者
The Mass Spectrometry Society of Japan
雑誌
Mass Spectrometry (ISSN:2187137X)
巻号頁・発行日
vol.11, no.1, pp.A0108, 2022-12-20 (Released:2022-12-20)
参考文献数
24
被引用文献数
1 2

We have developed a rapid and sensitive analytical method for α-tocopherol and its oxidative products by combining online hyphenation of supercritical fluid extraction-supercritical fluid chromatography (SFC) with proton transfer reaction (PTR) ionization mass spectrometry (MS). α-Tocopherol is a well-known antioxidant that plays a vital role in the antioxidant defense system in plant cells. However, studies on the cellular mechanisms of α-tocopherol have been limited owing to the lack of a rapid analytical method, which limits the comparison of plant cells incubated in various conditions. Additionally, complex sample preparation and long chromatography separation times are required. Moreover, the majority of the involved molecules are a combination of isomers, which must be separated before applying tandem MS. α-Tocopherol produces the α-tocopheroxyl radical in the first step of its antioxidant function; another ion with the same mass may also be generated from the source. SFC separation effectively distinguished the observed ions from their oxidative products in the sample and those produced during the ionization reaction process. This method enabled the measurement of α-tocopherol and its oxidative products such as α-tocopheroxyl radical and α-tocopheryl quinone in approximately 3 min per sample, including the time required for sample preparation.
著者
Yoshinao Wada Nobuhiko Okamoto
出版者
The Mass Spectrometry Society of Japan
雑誌
Mass Spectrometry (ISSN:2187137X)
巻号頁・発行日
vol.11, no.1, pp.A0103, 2022-04-15 (Released:2022-04-15)
参考文献数
13
被引用文献数
1 3

Electrospray ionization (ESI) mass spectrometry of transferrin can be used to diagnose congenital disorders of glycosylation (CDG) by detecting abnormal N-glycosylation due to reduced site occupancy or processing failure. Time-of-flight mass spectrometers are widely used to separate 25–45 charged ions in the m/z 1,700–3,000 range, and a summed zero-charge mass distribution is generated despite the risk of improper deconvolution. In this study, the low m/z region of the multiply-charged ion mass spectrum enabled a robust analysis of CDG. A triple quadrupole mass spectrometer, the standard instrument for newborn screening for inborn errors of metabolism, permitted the identification of the key ions characteristic of different types of CDG affecting PMM2, ALG14, SLC35A1, SLC35A2, MAN1B1 and PGM1 in the m/z 1,970–2,000 region. Charge deconvolution was used as a complementary tool for validating the findings. It was necessary to set a cutoff level for the evaluation, since small peaks indicating glycosylation failure or reduced sialylation were observed, even in control subjects. This method and workflow facilitates the implementation of MS-based analyses and the screening of CDG in clinical laboratories.
著者
Yoshinao Wada Nobuhiko Okamoto
出版者
The Mass Spectrometry Society of Japan
雑誌
Mass Spectrometry (ISSN:2187137X)
巻号頁・発行日
vol.11, no.1, pp.A0104, 2022-08-10 (Released:2022-08-10)
参考文献数
30
被引用文献数
2

Congenital disorders of glycosylation (CDG) are inherited metabolic diseases that affect the synthesis of glycoconjugates. Defects in mucin-type O-glycosylation occur independently or in combination with N-glycosylation disorders, and the profiling of the O-glycans of apolipoprotein CIII (apoCIII) by mass spectrometry (MS) can be used to support a diagnosis. The biomarkers are site occupancy and sialylation levels, which are indicated by the content of non-glycosylated apoCIII0a isoform and by the ratio of monosialylated apoCIII1 to disialylated apoCIII2 isoforms, respectively. In this report, electrospray ionization (ESI) quadrupole MS of apoCIII was used to identify these biomarkers. Among the instrumental parameters, the declustering potential (DP) induced the fragmentation of the O-glycan moiety including the Thr–GalNAc linkage, resulting in an increase in apoCIII0a ions. This incurs the risk of creating a false positive for reduced site occupancy. The apoCIII1/apoCIII2 ratio was substantially unchanged despite some dissociation of sialic acids. Therefore, appropriate DP settings are especially important when transferrin, which requires a higher DP, for N-glycosylation disorders is analyzed simultaneously with apoCIII in a single ESI MS measurement. Finally, a reference range of diagnostic biomarkers and mass spectra of apoCIII obtained from patients with SLC35A1-, TRAPPC11-, and ATP6V0A2-CDG are presented.

1 0 0 0 OA イオン光学

著者
松田 久
出版者
The Mass Spectrometry Society of Japan
雑誌
Journal of the Mass Spectrometry Society of Japan (ISSN:13408097)
巻号頁・発行日
vol.12, no.25, pp.47-58, 1964-05-30 (Released:2010-06-28)
参考文献数
11
被引用文献数
2 2

最近は2次の収束性をもつ質量分析器や,従来用いられてきた一様磁場,円筒電場以外の非一様磁場やトロイダル電場を用いた質量分析器の議論が盛になってきている。このような質量分析器を設計したり理解したりするにはイオン光学の知識がなければならないが,わが国にはこれに関する入門書がほとんどないので,非才を省みずイオン光学の概要をまとめてみた。問題をできるだけ平易に解析的にとりあげるようにしたので,すこし長たらしくなったきらいはあるが,初歩の微積分と力学の知識があれば御理解いただけるものと考えている。第1篇で1次近似の結果を,第2篇で2次の収差について,第3篇で端縁場の影響について述べる予定である。
著者
Tohru Yamagaki Kohtaro Sugahara Kohki Fujikawa Kazuto Washida
出版者
The Mass Spectrometry Society of Japan
雑誌
Mass Spectrometry (ISSN:2187137X)
巻号頁・発行日
vol.11, no.1, pp.A0101, 2022-02-28 (Released:2022-02-28)
参考文献数
16

Paeoniflorin and albiflorin, which are functional isomers, are the major constituents of an herbal medicine derived from Paeonia lactiflora. Those functional isomers and their galloylated derivatives, which are positional isomers, were studied by matrix-assisted laser desorption/ionization–tandem mass spectrometry (MALDI-MS/MS). The resulting mass spectra are discussed based on the fragmentation patterns of the sodium adducts. The product ion spectra of 4-O-galloylalbiflorin and 4′-O-galloylpaeoniflorin differed, even though they were positional isomers. The fragmentations of the ester parts were influenced by the neighboring hydroxyl groups. The ionization efficiency of the sodium adduct of albiflorin was higher than that for paeoniflorin. These results indicate that the carboxylic ester group has a higher affinity for sodium ions than the acetal group, which can be attributed to the carbonyl oxygen being negatively polarized, allowing it to function as a Lewis base.
著者
Hiroki Kannen Yuto Miyoshi Hisanao Hazama Kunio Awazu
出版者
The Mass Spectrometry Society of Japan
雑誌
Mass Spectrometry (ISSN:2187137X)
巻号頁・発行日
vol.10, no.1, pp.A0099, 2021-12-23 (Released:2021-12-23)
参考文献数
22

Mass spectrometry imaging (MSI) without labeling has the potential for faster screening in drug development. Matrix-assisted laser desorption/ionization (MALDI) is typically used, but it has a large matrix size and uneven drug distribution. Surface-assisted laser desorption/ionization (SALDI) using nanoparticles (NPs) may overcome these issues. Here, the influence of NPs, solvent ratio, and order of dropping of NPs on SALDI-MSI of protoporphyrin IX (PpIX), a cancer drug, are reported. A solution of PpIX in a 50% aqueous solution of 50% acetonitrile at a concentration of 10 μM was used. The NPs include ZnO, Fe3O4, and four types of TiO2. The NPs were fabricated by dissolving them on an aqueous 90% acetonitrile solution. Mass spectra were obtained with a time-of-flight mass spectrometer using a Nd:YAG laser at a 355-nm wavelength. The signal intensity using TiO2 at a 0.5 mg/mL concentration in 50% acetonitrile was increased by 1.6-fold compared to that without TiO2. Changing the solvent to 90% acetonitrile gave a uniform TiO2 distribution and a 9-fold increase in the signal intensity for PpIX. Among the four types of TiO2 with different particle sizes and crystal structures, TiO2 with a smaller particle size and a rutile crystal structure produced the highest signal intensity. Forming a layer on top of the PpIX also resulted in an increased signal intensity. Hence, SALDI using TiO2 provides effective ionization of the drug. In the future, we plan to investigate a spray method for the ionization of PpIX using TiO2 for the MSI of various drugs.
著者
Kanako Inoue Akimasa Fujihara
出版者
The Mass Spectrometry Society of Japan
雑誌
Mass Spectrometry (ISSN:2187137X)
巻号頁・発行日
vol.10, no.1, pp.A0097, 2021-09-07 (Released:2021-09-07)
参考文献数
33
被引用文献数
1

The enantioselectivity of tryptophan (Trp) for amino acids, such as alanine (Ala), valine (Val), and serine (Ser), was investigated using ultraviolet (UV) photoexcitation and tandem mass spectrometry. Product ion spectra of cold gas-phase amino acid enantiomers that were hydrogen-bonded to Na+(L-Trp) were measured using a variable-wavelength UV laser and a tandem mass spectrometer equipped with an electrospray ionization source and a cold ion trap. Na+(L-Trp), formed via amino acid detachment, and the elimination of CO2 from the clusters were observed in the product ion spectra. For photoexcitation at 265 nm, the relative abundance of Na+(L-Trp) compared to that of the precursor ion observed in the product ion spectrum of heterochiral Na+(L-Trp)(D-Ala) was larger than that observed in the product ion spectrum of homochiral Na+(L-Trp)(L-Ala). A difference between the Val enantiomers in the relative abundance of the precursor and product ions was observed in the case of photoexcitation at 272 nm. The elimination of CO2 was not observed for L-Ser for the 285 nm photoexcitation, which was the main reaction pathway for D-Ser. Photoexcited Trp chiral recognition was applied to identify and quantify the amino acid enantiomers in solution. Ala, Val, and Ser enantiomers in solution were quantified from their relative abundances in single product ion spectra measured using photoexcitation at 265, 272, and 285 nm, respectively, for hydrogen-bonded Trp within the clusters.
著者
Yoichi Otsuka
出版者
The Mass Spectrometry Society of Japan
雑誌
Mass Spectrometry (ISSN:2187137X)
巻号頁・発行日
vol.10, no.1, pp.A0095, 2021-06-30 (Released:2021-06-30)
参考文献数
212
被引用文献数
4

A combination of direct liquid extraction using a small volume of solvent and electrospray ionization allows the rapid measurement of complex chemical components in biological samples and visualization of their distribution in tissue sections. This review describes the development of such techniques and their application to biological research since the first reports in the early 2000s. An overview of electrospray ionization, ion suppression in samples, and the acceleration of specific chemical reactions in charged droplets is also presented. Potential future applications for visualizing multimolecular environments in biological systems are discussed.
著者
Hiromori Murashima Akimasa Fujihara
出版者
The Mass Spectrometry Society of Japan
雑誌
Mass Spectrometry (ISSN:2187137X)
巻号頁・発行日
vol.10, no.1, pp.A0096, 2021-06-10 (Released:2021-06-10)
参考文献数
22
被引用文献数
1

The gas-phase adsorption of N2 on protonated serine (Ser, C3H7NO3), threonine (Thr, C4H9NO3), glycine (Gly, C2H5NO2), and 2-aminoethanol (C2H7NO) was investigated using a tandem mass spectrometer equipped with an electrospray ionization source and a cold ion trap. N2 molecules were adsorbed on the free X–H (X=O and N) groups of protonated molecules. Gas-phase N2 adsorption-mass spectrometry detected the presence of free X–H groups in the molecular structures, and was applied to the structural elucidation of small molecules. When the 93 structures with an elemental composition of C3H7NO3 were filtered using the gas-phase N2 adsorption-mass spectrometry results for Ser, the number of possible molecular structures was reduced to 8 via the quantification of the X–H groups. Restricting and minimizing the number of possible candidates were effective steps in the structural elucidation process. Gas-phase N2 adsorption-mass spectrometry combined with mass spectrometry-based techniques has the potential for being useful for elucidating the molecular structures of a variety of molecules.
著者
Kenzo Hiraoka Osamu Ariyada Dilshadbek T. Usmanov Lee C. Chen Satoshi Ninomiya Kentaro Yoshimura Sen Takeda Zhang Yu Mridul K. Mandal Hiroshi Wada Stephanie Rankin-Turner Hiroshi Nonami
出版者
The Mass Spectrometry Society of Japan
雑誌
Mass Spectrometry (ISSN:2187137X)
巻号頁・発行日
vol.9, no.1, pp.A0092, 2020-12-04 (Released:2020-12-04)
参考文献数
61
被引用文献数
17

In 2007, probe electrospray ionization/mass spectrometry (PESI/MS) was developed. In this technique, the needle is moved down along a vertical axis and the tip of the needle touched to the sample. After capturing the sample at the needle tip, the needle is then moved up and a high voltage is applied to the needle at the highest position to generate electrospray. Due to the discontinuous sampling followed by the generation of spontaneous electrospray, sequential and exhaustive electrospray takes place depending on the surface activity of the analytes. As modified versions of PESI, dipping PESI (dPESI), sheath-flow PESI (sfPESI) and adjustable sfPESI (ad-sfPESI) have been developed. These methods are complementary to each other and they can be applicable to surface and bulk analysis of various biological samples. In this article, the characteristics of these methods and their applications to real samples will be reviewed.
著者
Hiroki Kannen Shusei Nomura Hisanao Hazama Yasufumi Kaneda Tatsuya Fujino Kunio Awazu
出版者
The Mass Spectrometry Society of Japan
雑誌
Mass Spectrometry (ISSN:2187137X)
巻号頁・発行日
vol.9, no.1, pp.A0091, 2020-12-04 (Released:2020-12-04)
参考文献数
20
被引用文献数
1

Combined therapy using photodynamic therapy (PDT) and chemotherapy has been proposed for anticancer-drug-resistant cancer cells. To evaluate the efficacy of such a combined therapy, the uptakes of an anticancer drug and a photosensitizer in cancer cells must be assessed. Mass spectrometry using matrix-assisted laser desorption/ionization can detect multiple drugs simultaneously. Human prostate cancer cells PC-3 or docetaxel-resistant cancer cells PC-3-DR were incubated in a serum-free medium containing a photosensitizer, protoporphyrin IX (PpIX), and an anticancer drug, docetaxel. A zeolite matrix was created by mixing 6-aza-2-thiothymine and NaY5.6 zeolite, and dissolving in water with 50% acetone. Ions were obtained with a time-of-flight mass spectrometer using a Nd:YAG laser at a wavelength of 355 nm. The cell morphology was preserved by washing the cells with ammonium acetate and drying in a vacuum after drug administration. Protonated PpIX (m/z 563.3) and the sodium adduct ion of docetaxel (m/z 829.9) were obtained from PC-3 cells simultaneously using the zeolite matrix. On the other hand, PpIX was detected but ions originating from docetaxel were not detected from PC-3-DR cells. The result indicated the efficacy of PDT for docetaxel-resistant cancer cells.
著者
Kazumi Saikusa Haruna Hidaka Shunsuke Izumi Satoko Akashi
出版者
The Mass Spectrometry Society of Japan
雑誌
Mass Spectrometry (ISSN:2187137X)
巻号頁・発行日
vol.9, no.1, pp.A0090, 2020-10-31 (Released:2020-10-31)
参考文献数
30
被引用文献数
1

Post-translational modifications (PTMs) of histone N-terminal tails in nucleosome core particle (NCP), such as acetylation, play crucial roles in regulating gene expression. To unveil the regulation mechanism, atomic-level structural analysis of in-vitro modified NCP is effective with verifying the PTMs of histones. So far, identification of PTMs of NCP originating from living cells has mainly been performed using mass spectrometry (MS) techniques, such as bottom-up approach. The bottom-up approach is the most established method for protein characterization, but it does not always provide sufficient information on the acetylated sites of lysine residues in the histone tails if trypsin digestion is carried out. For histone proteins, which have many basic amino acids, trypsin generates too many short fragments that cannot be perfectly analyzed by tandem MS. In this study, we investigated the in vitro acetylation sites in the histone H3 tail using a top-down sequence analysis, matrix-assisted laser desorption/ionization in-source decay (MALDI-ISD) experiment, in combination with aminopeptidase digestion. Aminopeptidase can cleave peptide bonds one-by-one from the N-terminus of peptides or proteins, generating N-terminally truncated peptides and/or proteins. As a result, it was identified that this method enables sequence characterization of the entire region of the H3 tail. Also, application of this method to H3 in in-vitro acetylated NCP enabled assigning acetylation sites of H3. Thus, this method was found to be effective for obtaining information on in-vitro acetylation of NCP for structural biology study.
著者
Adinda Putri Wisman Yoshihiro Tamada Shuji Hirohata Eiichiro Fukusaki Shuichi Shimma
出版者
The Mass Spectrometry Society of Japan
雑誌
Mass Spectrometry (ISSN:2187137X)
巻号頁・発行日
vol.9, no.1, pp.A0089, 2020-08-26 (Released:2020-08-26)
参考文献数
26
被引用文献数
8

The compounds inside rice koji have been thoroughly investigated as an essential material in making many food-related products, including sake. However, these studies focused only on quantitative aspects, leaving features that can still be uncovered if seen from a new perspective. Visualization of the metabolites inside rice koji may as well be the new angle needed to retrieve more information regarding rice koji making. Here we utilized mass spectrometry imaging (MSI) to visualize the distribution of sugars, sugar alcohols, and amino acids inside rice koji. Imaging results revealed that several sugars alcohols and amino acids were shown to have characteristic distribution near the edges or surface of rice koji. Furthermore, the distribution appears to be correlated with the different structure of rice koji. This study is the first report of using MSI to visualize sugars, sugar alcohols, and amino acids in rice koji.
著者
Shuichi Shimma Yoshiki Makino Kazuto Kojima Takafumi Hirata
出版者
The Mass Spectrometry Society of Japan
雑誌
Mass Spectrometry (ISSN:2187137X)
巻号頁・発行日
vol.9, no.1, pp.A0086, 2020-07-13 (Released:2020-07-13)
参考文献数
19
被引用文献数
1

Platinum, a transition metal that is widely used in anti-cancer agents, also results in the development of nephropathy due to severe adverse reactions caused by platinum-induced nephrotoxicity. Reports on imaging with metals other than platinum remain are limited, even in preclinical studies. Furthermore, most of these are case reports, and the relationship between the distribution of the metal and clinical observations in human samples is not well understood. Here we report on visualizing lanthanum (139La), a component of Fosrenol, which is usually used for the treatment of hyperphosphatemia. Gastric inflammation, also known as hemorrhagic gastritis, is the main adverse event caused by Fosrenol. To conduct this study, 139La was visualized in gastric biopsy samples obtained from a patient using quantitative laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). We also compared the distribution of 139La in tissue and histochemical results. The areas where 139La accumulated corresponded to the macrophage-positive areas observed in immunohistochemistry studies using an anti-CD68 antibody. In contrast, we observed a debris-like crystal morphology in hematoxylin and eosin staining tissues. The debris was also associated with 139La accumulation. The abnormal accumulation of 139La crystals caused the observed inflammation. This phenomenon was previously characterized, but this is the first report in which 139La distribution and histochemical results are compared using LA-ICP-MS.
著者
Yoshinao Wada
出版者
The Mass Spectrometry Society of Japan
雑誌
Mass Spectrometry (ISSN:2187137X)
巻号頁・発行日
vol.9, no.1, pp.A0084, 2020-04-23 (Released:2020-04-23)
参考文献数
27
被引用文献数
7

Congenital disorders of glycosylation (CDG), an increasingly recognized group of diseases that affect glycosylation, comprise the largest known subgroup of approximately 100 responsible genes related to N-glycosylation. This subgroup presents various molecular abnormalities, of either the CDG-I or the CDG-II type, attributable to a lack of glycans or abnormal glycoform profiles, respectively. The most effective approach to identifying these N-glycosylation disorders is mass spectrometry (MS) using either released glycans, intact glycoproteins or proteolytic peptides as analytes. Among these, MS of tryptic peptides derived from transferrin can be used to reliably identify signature peptides that are characteristic of CDG-I and II. In the present study, matrix-assisted laser desorption/ionization (MALDI) MS was applied to various N-glycosylation disorders including ALG1-CDG, B4GALT1-CDG, SLC35A2-CDG, ATP6V0A2-CDG, TRAPPC11-CDG and MAN1B1-CDG. This method does not require the prior enrichment of glycopeptides or chromatographic separation, and thus serves as a practical alternative to liquid chromatography-electrospray ionization MS. The signature peptides are biomarkers of CDG.
著者
Naoyuki Sugiyama
出版者
The Mass Spectrometry Society of Japan
雑誌
Mass Spectrometry (ISSN:2187137X)
巻号頁・発行日
vol.9, no.1, pp.A0082, 2020-03-28 (Released:2020-03-28)
参考文献数
77
被引用文献数
2

Protein phosphorylation mediated by protein kinases is one of the most significant posttranslational modifications in many biological events. The function and physiological substrates of specific protein kinases, which are highly associated with known signal transduction elements or therapeutic targets, have been extensively studied using various approaches; however, most protein kinases have not yet been characterized. In recent decades, many techniques have been developed for the identification of in vitro and physiological substrates of protein kinases. In this review, I summarize recent studies profiling the characteristics of kinases using mass spectrometry-based proteomics, focusing on the large-scale identification of in vitro substrates of the human kinome using a quantitative phosphoproteomics approach.