共查询到20条相似文献,搜索用时 15 毫秒
1.
Virginie Domalain Vincent Tognetti Marie Hubert-Roux Catherine M. Lange Laurent Joubert Jérôme Baudoux Jacques Rouden Carlos Afonso 《Journal of the American Society for Mass Spectrometry》2013,24(9):1437-1445
Stereochemistry plays an important role in biochemistry, particularly in therapeutic applications. Indeed, enantiomers have different biological activities, which can have important consequences. Many analytical techniques have been developed in order to allow the identification and the separation of stereoisomers. Here, we focused our work on the study of small diastereomers using the coupling of traveling wave ion mobility and mass spectrometry (TWIMS-MS) as a new alternative for stereochemistry study. In order to optimize the separation, the formation of adducts between diastereomers (M) and different alkali cations (X) was carried out. Thus, monomers [M + X]+ and multimers [2M + X]+ and [3M + X]+ ions have been studied from both experimental and theoretical viewpoints. Moreover, it has been shown that the study of the multimer [2Y + M + Li]+ ion, in which Y is an auxiliary diastereomeric ligand, allows the diastereomers separation. The combination of cationization, multimers ions formation, and IM-MS is a novel and powerful approach for the diastereomers identification. Thus, by this technique, diastereomers can be identified although they present very close conformations in gaseous phase. This work presents the first TWIMS-MS separation of diastereomers, which present very close collision cross section thanks to the formation of multimers and the use of an auxiliary diastereomeric ligand. Figure
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2.
Carly N. Ferguson Ashley C. Gucinski-Ruth 《Journal of the American Society for Mass Spectrometry》2016,27(5):822-833
Analytical techniques capable of detecting changes in structure are necessary to monitor the quality of monoclonal antibody drug products. Ion mobility mass spectrometry offers an advanced mode of characterization of protein higher order structure. In this work, we evaluated the reproducibility of ion mobility mass spectrometry measurements and mobiligrams, as well as the suitability of this approach to differentiate between and/or characterize different monoclonal antibody drug products. Four mobiligram-derived metrics were identified to be reproducible across a multi-day window of analysis. These metrics were further applied to comparative studies of monoclonal antibody drug products representing different IgG subclasses, manufacturers, and lots. These comparisons resulted in some differences, based on the four metrics derived from ion mobility mass spectrometry mobiligrams. The use of collision-induced unfolding resulted in more observed differences. Use of summed charge state datasets and the analysis of metrics beyond drift time allowed for a more comprehensive comparative study between different monoclonal antibody drug products. Ion mobility mass spectrometry enabled detection of differences between monoclonal antibodies with the same target protein but different production techniques, as well as products with different targets. These differences were not always detectable by traditional collision cross section studies. Ion mobility mass spectrometry, and the added separation capability of collision-induced unfolding, was highly reproducible and remains a promising technique for advanced analytical characterization of protein therapeutics. 相似文献
3.
Bornschein RE Hyung SJ Ruotolo BT 《Journal of the American Society for Mass Spectrometry》2011,22(10):1690-1698
Characterizing intact multiprotein complexes in terms of both their mass and size by ion mobility-mass spectrometry is becoming
an increasingly important tool for structural biology. Furthermore, the charge states of intact protein complexes can dramatically
influence the information content of gas-phase measurements performed. Specifically, protein complex charge state has a demonstrated
influence upon the conformation, mass resolution, ion mobility resolution, and dissociation properties of protein assemblies
upon collisional activation. Here we present the first comparison of charge-reduced multiprotein complexes generated by solution
additives and gas-phase ion-neutral reaction chemistry. While the charge reduction mechanism for both methods is undoubtedly
similar, significant gas-phase activation of the complex is required to reduce the charge of the assemblies generated using
the solution additive strategy employed here. This activation step can act to unfold intact protein complexes, making the
data difficult to correlate with solution-phase structures and topologies. We use ion mobility-mass spectrometry to chart
such conformational effects for a range of multi-protein complexes, and demonstrate that approaches to reduce charge based
on ion-neutral reaction chemistry in the gas-phase consistently produce protein assemblies having compact, ‘native-like’ geometries
while the same molecules added in solution generate significantly unfolded gas-phase complexes having identical charge states. 相似文献
4.
Spencer A. Prost Kevin L. Crowell Erin S. Baker Yehia M. Ibrahim Brian H. Clowers Matthew E. Monroe Gordon A. Anderson Richard D. Smith Samuel H. Payne 《Journal of the American Society for Mass Spectrometry》2014,25(12):2020-2027
Applying Hadamard transform multiplexing to ion mobility separations (IMS) can significantly improve the signal-to-noise ratio and throughput for IMS coupled mass spectrometry (MS) measurements by increasing the ion utilization efficiency. However, it has been determined that fluctuations in ion intensity as well as spatial shifts in the multiplexed data lower the signal-to-noise ratios and appear as noise in downstream processing of the data. To address this problem, we have developed a novel algorithm that discovers and eliminates data artifacts. The algorithm employs an analytical approach to identify and remove artifacts from the data, decreasing the likelihood of false identifications in subsequent data processing. Following application of the algorithm, IMS-MS measurement sensitivity is greatly increased and artifacts that previously limited the utility of applying the Hadamard transform to IMS are avoided. Figure
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5.
6.
Joseph D. Eschweiler Aaron T. Frank Brandon T. Ruotolo 《Journal of the American Society for Mass Spectrometry》2017,28(10):1991-2000
Multiprotein complexes are central to our understanding of cellular biology, as they play critical roles in nearly every biological process. Despite many impressive advances associated with structural characterization techniques, large and highly-dynamic protein complexes are too often refractory to analysis by conventional, high-resolution approaches. To fill this gap, ion mobility-mass spectrometry (IM-MS) methods have emerged as a promising approach for characterizing the structures of challenging assemblies due in large part to the ability of these methods to characterize the composition, connectivity, and topology of large, labile complexes. In this Critical Insight, we present a series of bioinformatics studies aimed at assessing the information content of IM-MS datasets for building models of multiprotein structure. Our computational data highlights the limits of current coarse-graining approaches, and compelled us to develop an improved workflow for multiprotein topology modeling, which we benchmark against a subset of the multiprotein complexes within the PDB. This improved workflow has allowed us to ascertain both the minimal experimental restraint sets required for generation of high-confidence multiprotein topologies, and quantify the ambiguity in models where insufficient IM-MS information is available. We conclude by projecting the future of IM-MS in the context of protein quaternary structure assignment, where we predict that a more complete knowledge of the ultimate information content and ambiguity within such models will undoubtedly lead to applications for a broader array of challenging biomolecular assemblies. 相似文献
7.
Jung JE Pierson NA Marquardt A Scheffner M Przybylski M Clemmer DE 《Journal of the American Society for Mass Spectrometry》2011,22(8):1463-1471
Modification of ubiquitin, a key cellular regulatory polypeptide of 76 amino acids, to polyubiquitin conjugates by lysine-specific
isopeptide linkage at one of its seven lysine residues has been recognized as a central pathway determining its biochemical
properties and cellular functions. Structural details and differences of distinct lysine-isopeptidyl ubiquitin conjugates
that reflect their different functions and reactivities, however, are only partially understood. Ion mobility spectrometry
(IMS) combined with mass spectrometry (MS) has recently emerged as a powerful tool for probing conformations and topology
involved in protein interactions by an electric field-driven separation of polypeptide ions through a drift gas. Here we report
the conformational characterization and differentiation of Lys63- and Lys48-linked ubiquitin conjugates by IMS–MS. Lys63-
and Lys48-linked di-ubiquitin conjugates were prepared by recombinant bacterial expression and by chemical synthesis using
a specific chemical ligation strategy, and characterized by high-resolution Fourier transform ion cyclotron resonance mass
spectrometry, circular dichroism spectroscopy, and molecular modeling. IMS–MS was found to be an effective tool for the identification
of structural differences of ubiquitin complexes in the gas phase. The comparison of collision cross-sections of Lys63- and
Lys48-linked di-ubiquitin conjugates showed a more elongated conformation of Lys63-linked di-ubiquitin. In contrast, the Lys48-linked
di-ubiquitin conjugate showed a more compact conformation. The IMS-MS results are consistent with published structural data
and a comparative molecular modeling study of the Lys63- and Lys48-linked conjugates. The results presented here suggest IMS
techniques can provide information that complements MS measurements in differentiating higher-order polyubiquitins and other
isomeric protein linkages. 相似文献
8.
Ma Q Wang C Bai H Xi HW Xi GC Ren XM Yang Y Guo LH 《Journal of the American Society for Mass Spectrometry》2011,22(10):1851-1861
A comprehensive two-dimensional system coupling ultra-performance liquid chromatography (UPLC) and ion mobility-mass spectrometry
(IM-MS) has been applied for the separation and analysis of hydroxylated polybrominated diphenyl ethers (OH-PBDEs). A complex
mixture containing 23 OH-PBDE congeners ranging from hydroxylated monobromodiphenyl ether (OH-monoBDE) to hydroxylated octabromodiphenyl
ether (OH-octaBDE) was satisfactorily separated within 16 min of analysis time. The first-dimensional reversed-phase UPLC
was performed on a sub-2 μm BEH C18 chromatographic column using acetonitrile-water gradient elution program with a flow rate ramp. It enabled excellent chromatographic
separation for both between-class and within-class OH-PBDEs based on their differences in hydrophobicity. Following the pre-ionization
resolution in the first dimension, the second-dimensional IM-MS employed a hybrid electrospray quadrupole ion mobility time-of-flight
mass spectrometer and added an extra post-ionization separation for between-class OH-PBDE congeners on account of their relative
mobility disparity during a very short period of 8.80 ms. The orthogonality of the developed two-dimensional system was evaluated
with the correlation coefficient of 0.9665 and peak spreading angle of 14.87°. The peak capacity of the system was calculated
to be approximately 2 and 15 times higher than that of the two dimensions used alone, respectively. The two-dimensional separation
plane also contributed to the removal of background interference ions and the enhanced confidence in the characterization
of OH-PBDEs of interest. 相似文献
9.
10.
Asia Al-jabiry Dr. Martin Palmer Dr. James Langridge Dr. Jeddidiah Bellamy-Carter Dr. David Robinson Prof. Neil J. Oldham 《Chemistry (Weinheim an der Bergstrasse, Germany)》2021,27(55):13783-13792
Native mass spectrometry is now an important tool in structural biology. Thus, the nature of higher protein structure in the vacuum of the mass spectrometer is an area of significant interest. One of the major goals in the study of gas-phase protein structure is to elucidate the stabilising role of interactions at the level of individual amino acid residues. A strategy combining protein chemical modification together with collision induced unfolding (CIU) was developed and employed to probe the structure of compact protein ions produced by native electrospray ionisation. Tractable chemical modification was used to alter the properties of amino acid residues, and ion mobility-mass spectrometry (IM-MS) utilised to monitor the extent of unfolding as a function of modification. From these data the importance of specific intramolecular interactions for the stability of compact gas-phase protein structure can be inferred. Using this approach, and aided by molecular dynamics simulations, an important stabilising interaction between K6 and H68 in the protein ubiquitin was identified, as was a contact between the N-terminus and E22 in a ubiquitin binding protein UBA2. 相似文献
11.
Philippe Massonnet Jean R. N. Haler Gregory Upert Michel Degueldre Denis Morsa Nicolas Smargiasso Gilles Mourier Nicolas Gilles Loïc Quinton Edwin De Pauw 《Journal of the American Society for Mass Spectrometry》2016,27(10):1637-1646
Disulfide bonds are post-translationnal modifications that can be crucial for the stability and the biological activities of natural peptides. Considering the importance of these disulfide bond-containing peptides, the development of new techniques in order to characterize these modifications is of great interest. For this purpose, collision cross cections (CCS) of a large data set of 118 peptides (displaying various sequences) bearing zero, one, two, or three disulfide bond(s) have been measured in this study at different charge states using ion mobility-mass spectrometry. From an experimental point of view, CCS differences (ΔCCS) between peptides bearing various numbers of disulfide bonds and peptides having no disulfide bonds have been calculated. The ΔCCS calculations have also been applied to peptides bearing two disulfide bonds but different cysteine connectivities (Cys1-Cys2/Cys3-Cys4; Cys1-Cys3/Cys2-Cys4; Cys1-Cys4/Cys2-Cys3). The effect of the replacement of a proton by a potassium adduct on a peptidic structure has also been investigated. 相似文献
12.
Daniel N. Mortensen Anna C. Susa Evan R. Williams 《Journal of the American Society for Mass Spectrometry》2017,28(7):1282-1292
A method for relating traveling-wave ion mobility spectrometry (TWIMS) drift times with collisional cross-sections using computational simulations is presented. This method is developed using SIMION modeling of the TWIMS potential wave and equations that describe the velocity of ions in gases induced by electric fields. The accuracy of this method is assessed by comparing the collisional cross-sections of 70 different reference ions obtained using this method with those obtained from static drift tube ion mobility measurements. The cross-sections obtained here with low wave velocities are very similar to those obtained using static drift (average difference?=?0.3%) for ions formed from both denaturing and buffered aqueous solutions. In contrast, the cross-sections obtained with high wave velocities are significantly greater, especially for ions formed from buffered aqueous solutions. These higher cross-sections at high wave velocities may result from high-order factors not accounted for in the model presented here or from the protein ions unfolding during TWIMS. Results from this study demonstrate that collisional cross-sections can be obtained from single TWIMS drift time measurements, but that low wave velocities and gentle instrument conditions should be used in order to minimize any uncertainties resulting from high-order effects not accounted for in the present model and from any protein unfolding that might occur. Thus, the method presented here eliminates the need to calibrate TWIMS drift times with collisional cross-sections measured using other ion mobility devices. 相似文献
13.
Quantitative determination of the elemental composition of metals and other solids by glow discharge mass spectrometry requires a calibration factor for each element. In past work, these factors, called relative ion yields (RIYs), have been determined experimentally from the mass spectra of standards of certified composition. The RlYs of some elements were found to be over 10 times larger than the RIYs of other elements. In this study a simple calculation of the RIYs of the elements within the same sample is derived from a theoretical framework which takes into account the combined effects of sputtering and ionization. The ionization function involves the electron affinity and the first ionization potential of each element, plus two unknown parameters. By favorable selection of a temperature parameter and a chemical-potential parameter, the RIYs calculated by this method were found to agree satisfactorily with the experimental RlYs of former work. The temperature of 16,000 K (used in this work) corresponds to an average electron energy of ~ 2 eV. 相似文献
14.
利用激光溅射-分子束的方法研究了Al+和乙硫醇的气相化学反应,结果观察到了Al+与1~6个乙硫醇分子形成的团簇离子. 对团簇离子进行了密度泛函理论计算,找到了两种类型的异构体Al+(C2H5SH)n和HAl+SC2H5(C2H5SH)n-1,计算得到了相应的稳定结构和能量.分析质谱信号强度,结合理论计算结果,可推测出实验得到的n=1的产物离子是Al+(C2H5SH). n=2和3时产物离子开始转变为HAl+SC2H5(C2H5SH)n-1, n=4时,HAl+SC2H5(C2H5SH)3和Al+(C2H5SH)4两种产物离子都存在,n≥5以后,团簇离子Al+(C2H5SH)n开始成为主要的产物离子. 相似文献
15.
16.
Rafael A. Cherkasov Vladimir I. Galkin Galina A. Chmutova Nina A. Polezhaeva Irina V. Kalinina Arcady N. Pudovik 《Phosphorus, sulfur, and silicon and the related elements》2013,188(6-7):1717-1719
The phosphorylation reactions of the oxygen- and nitrogen-containing halocyclenes--3,4-dichloro-5-hydroxyfuranone, 3,4-dichloro-5-substi- tuted pyrrolinon-2-ones and N-phenyl-4,5 dichloropyridazin-2-one by 3 -phosphorus compounds--trialkylphoshphites, triphenylphosphine, and some P-functionalized derivatives of the trivalent phosphorus are studied. The reactions' mechanisms are discussed; the possible and preferable reactions' routes and the relative thermodynamic stabilities of the products and intermediates are estimated via the quantum-chemical methods. 相似文献
17.
Henryk Wincel 《Journal of the American Society for Mass Spectrometry》2014,25(12):2134-2142
Hydration reactions of protonated and sodiated thiouracils (2-thiouracil, 6-methyl-2-thiouracil, and 4-thiouracil) generated by electrospray ionization have been studied in a gas phase at 10 mbar using a pulsed ion-beam high-pressure mass spectrometer. The thermochemical data, ΔH o n, ΔS o n, and ΔG o n, for the hydrated systems were obtained by equilibrium measurements. The water binding energies of protonated thiouracils, [2SU]H+ and [6Me2SU]H+, were found to be of the order of 51 kJ/mol for the first, and 46 kJ/mol for the second water molecule. For [4SU]H+, these values are 3–4 kJ/mol lower. For sodiated complexes, these energies are similar for all studied systems, and varied between 62 and 68 kJ/mol for the first and between 48 and 51 kJ/mol for the second water molecule. The structural aspects of the precursors for hydrated complexes are discussed in conjunction with available literature data. Graphical Abstract
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18.
Anastasia V. Shishkina Alexander A. Ksenofontov Nikita V. Penkov Mikhail V. Vener 《Molecules (Basel, Switzerland)》2022,27(10)
Self-assembly of organic ions in aqueous solutions is a hot topic at the present time, and substances that are well-soluble in water are usually studied. In this work, aqueous solutions of sodium diclofenac are investigated, which, like most medicinal compounds, is poorly soluble in water. Classical MD modeling of an aqueous solution of diclofenac sodium showed equilibrium between the hydrated anion and the hydrated dimer of the diclofenac anion. The assignment and interpretation of the bands in the UV, NIR, and IR spectra are based on DFT calculations in the discrete-continuum approximation. It has been shown that the combined use of spectroscopic methods in various frequency ranges with classical MD simulations and DFT calculations provides valuable information on the association processes of medical compounds in aqueous solutions. Additionally, such a combined application of experimental and calculation methods allowed us to put forward a hypothesis about the mechanism of the effect of diclofenac sodium in high dilutions on a solution of diclofenac sodium. 相似文献
19.
Wu R Marta RA Martens JK Eldridge KR McMahon TB 《Journal of the American Society for Mass Spectrometry》2011,22(9):1651-1659
The structure of the proton-bound lysine dimer has been investigated by infrared multiple photon dissociation (IRMPD) spectroscopy
and electronic structure calculations. The structures of different possible isomers of the proton-bound lysine dimer have
been optimized at the B3LYP/6-31 + G(d) level of theory and IR spectra calculated using the same computational method. Based
on relative Gibbs free energies (298 K) calculated at the MP2/aug-cc-pVTZ//B3LYP/6-31 + G(d) level of theory, LL-CS01, and
followed closely (1.1 kJ mol–1) by LL-CS02 are the most stable non-zwitterionic isomers. At the MP2/aug-cc-pVTZ//6-31 + G(d) and MP2/aug-cc-pVTZ//6-31 + (d,p)
levels of theory, isomer LL-CS02 is favored by 3.0 and 2.3 kJ mol–1, respectively. The relative Gibbs free energies calculated by the aforementioned levels of theory for LL-CS01 and LL-CS02
are very close and strongly suggest that diagnostic vibrational signatures found in the IRMPD spectrum of the proton-bound
dimer of lysine can be attributed to the existence of both isomers. LL-ZW01 is the most stable zwitterionic isomer, in which
the zwitterionic structure of the neutral lysine is well stabilized by the protonated lysine moiety via a very strong intermolecular
hydrogen bond. At the MP2/aug-cc-pVTZ//B3LYP/6-31 + G(d), MP2/aug-cc-pVTZ//6-31 + G(d) and MP2/aug-cc-pVTZ//6-31 + G(d,p)
levels of theory, the most stable zwitterionic isomer (LL-ZW01) is less favored than LL-CS01 by 7.3, 4.1 and 2.3 kJ mol–1, respectively. The experimental IRMPD spectrum also confirms that the proton-bound dimer of lysine largely exists as charge-solvated
isomers. Investigation of zwitterionic and charge-solvated species of amino acids in the gas phase will aid in a further understanding
of structure, property, and function of biological molecules. 相似文献
20.
Carlo Tiebe Thomas Hübert Bernhard Koch Uwe Ritter Ina Stephan 《International Journal for Ion Mobility Spectrometry》2010,13(1):17-24
The metabolism of moulds results in the formation of various microbial volatile organic compounds (MVOCs). These substances
can be used as an indicator for the presence of moulds in the indoor environment. Three different mould strains were cultivated
on culture media and IMS spectra of gaseous mould metabolites were recorded using a portable mini system with a tritium source
and a 5 cm drift cell. The headspace spectra are characteristic for mould species and their age. Typical gaseous components
of the metabolites were identified and compared with results obtained from gas chromatography using a mass spectrometer detector.
It was observed that the MVOCs formation depends on mould species and their growing stage with a maximum of MVOCs emission
occurring during the first 10 days. These preliminary results show that IMS can be applied to detect MVOCs in indoor environment
and indicate hidden mould growth. 相似文献