Article
Chemistry, Analytical
Qingyu Hu, Yuting Sun, Xiyan Mu, Yulan Wang, Huiru Tang
Summary: Direct-infusion tandem mass spectrometry (DI-MS/MS) is valuable for quantitative metabolomics, MS imaging, and single cell studies, but cannot differentiate isomers/isobars with similar MS spectral features. In this study, the fragmentation pathways and characteristics of differential ion-mobility spectrometry (DMS) for four organic compounds were comprehensively investigated. A DI-DMS-MS/MS method was developed to simultaneously quantify these compounds. The method showed high accuracy and low limit-of-quantification, and clear differences between human and mouse urine samples were observed.
Article
Chemistry, Analytical
Anais C. George, Isabelle Schmitz-Afonso, Vincent Marie, Benoit Colsch, Francois Fenaille, Carlos Afonso, Corinne Loutelier-Bourhis
Summary: Collision cross sections (CCS) are important molecular descriptors in metabolomics and lipidomics analyses. Ion mobility spectrometry (IMS) can determine CCS, but different techniques require calibration and lead to varying results. This study evaluates 11 different CCS calibrants and proposes a method to recalibrate CCS values using Tune Mix solution for more accurate and comparable results.
ANALYTICA CHIMICA ACTA
(2022)
Article
Chemistry, Multidisciplinary
Sophie R. Harvey, Zachary L. VanAernum, Vicki H. Wysocki
Summary: Negative mode ionization of protein complexes offers closer-to-native structural information with avoided peak broadening caused by solution phase charge reduction additives. It also provides direct structural information when coupled with SID.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemical Research Methods
Joon-Yong Lee, Aivett Bilbao, Christopher R. Conant, Kent J. Bloodsworth, Daniel J. Orton, Mowei Zhou, Jesse W. Wilson, Xueyun Zheng, Ian K. Webb, Ailin Li, Kim K. Hixson, John C. Fjeldsted, Yehia M. Ibrahim, Samuel H. Payne, Christer Jansson, Richard D. Smith, Thomas O. Metz
Summary: AutoCCS is an open-source software for rapid determination of CCS values from IMS-MS measurements, demonstrating accuracy and reproducibility for standard and unknown analyte ions under various conditions.
Article
Biochemical Research Methods
Charles Eldrid, Aisha Ben-Younis, Jakub Ujma, Hannah Britt, Tristan Cragnolini, Symeon Kalfas, Dale Cooper-Shepherd, Nick Tomczyk, Kevin Giles, Mike Morris, Rehana Akter, Daniel Raleigh, Konstantinos Thalassinos
Summary: Ion mobility coupled to mass spectrometry (IM-MS) is widely utilized to study protein dynamics and structure in the gas phase. A high-resolution cyclic IM-mass spectrometer (cIM-MS) allows for multiple rounds of tandem IM experiments to be conducted, providing insights into protein unfolding pathways and dynamics. The IMn-MS technique shows evidence of interconversion between compact and extended protein structures, and suggests certain conformations have low energy barriers between them.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2021)
Article
Biochemical Research Methods
Elvin R. Cabrera, Brian H. Clowers
Summary: By casting ion population's mobility information in the frequency domain, time-dispersive ion mobility techniques can now be compatible with slower mass analyzers like ion traps. Recent progress has been made in maximizing the efficiency of Fourier transform ion mobility-mass spectrometry (FT-IM-MS) experiments, but the intersection between practical implementation considerations and theoretical limits of traditional signal processing techniques needs to be further explored. The importance of avoiding signal aliasing due to undersampling signals, along with evaluating limitations imposed by experimental parameters, is crucial for successful Fourier-based multiplexing experiments.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2022)
Article
Chemistry, Analytical
Daisy Unsihuay, Ruichuan Yin, Daniela Mesa Sanchez, Manxi Yang, Yingju Li, Xiaofei Sun, Sudhansu K. Dey, Julia Laskin
Summary: The study introduces a novel experimental platform that combines nano-DESI and IM spectrometry for high spatial resolution imaging of molecules in mouse uterine tissues, providing unique molecular descriptors and revealing variations in isomeric composition through isomer-specific imaging.
ANALYTICA CHIMICA ACTA
(2021)
Article
Microbiology
Kai P. Law, Wei He, Jianchang Tao, Chuanlun Zhang
Summary: Archaea are differentiated by the unique structure and composition of their lipids. Characterization of the lipidome remains technologically challenging due to the complexity and diversity of lipids. Developing novel analytical protocols is necessary to enhance lipidome coverage and provide insights into the adaptability of archaea to environmental stresses.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Agriculture, Multidisciplinary
Xue-Chao Song, Elena Canellas, Nicola Dreolin, Cristina Nerin, Jeff Goshawk
Summary: The study characterized and quantified phenolic compounds in bearberry leaves using IMS and a mass spectrometer, identifying 88 compounds including arbutin, tannins, flavanols, and flavonols. Arbutin, 1,2,3,4,6-pentagalloylglucose, and quercetin were the most abundant phenolic components in the leaves.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2021)
Article
Biochemical Research Methods
Alexis N. Edwards, Anthony J. Blue, Jessica M. Conforti, Michael S. Cordes, Michael A. Trakselis, Elyssia S. Gallagher
Summary: The biological role of the bacterial chloramphenicol (Chl)-resistance enzyme, chloramphenicol acetyltransferase (CAT), has been reevaluated. The gas-phase structure and thermodynamic stability of CAT have been investigated using ion mobility spectrometry-mass spectrometry (IMS-MS). It was found that CAT binds Chl and a non-hydrolyzable acetyl-CoA derivative (S-ethyl-CoA) without significant changes to its structure or stability. This study provides insights into the gas-phase unfolding and dissociation behavior of CAT and lays the foundation for further characterization of alternative substrates and inhibitors.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Analytical
K. Richardson, D. Langridge, S. M. Dixit, B. T. Ruotolo
Summary: The combination of ion-mobility (IM) separation with mass spectrometry (MS) has revolutionized global measurement efforts in various areas, including food analysis and drug discovery. Traveling Wave Ion Mobility (TWIM) devices, the first commercialized form of IM-MS, operate under low pressures and voltages, making them ideal for hybridization with MS. However, due to the complex motion of ions in TWIM devices, calibration of IM transit times is essential for accurate CCS measurements.
ANALYTICAL CHEMISTRY
(2021)
Article
Biochemical Research Methods
Arnold Steckel, Agnes Revesz, David Papp, Katalin Uray, Laszlo Drahos, Gitta Schlosser
Summary: Tandem mass spectrometry (MS/MS) is crucial for protein identification and quantification in proteomics. This study investigates the characteristics of MS/MS for reliable identification of citrullination, a PTM related to autoimmune diseases and cancer. The findings suggest adjusting collision energy settings and using specific software for accurate identification.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2022)
Article
Biochemical Research Methods
Mirela Sarbu, Ligia Petrica, David E. Clemmer, Zeljka Vukelic, Alina D. Zamfir
Summary: GBM is a malignant and highly aggressive brain tumor with aberrant cell-surface glycosylation patterns in nearly all tumor cells. Profiling of ganglioside mixtures from GBM specimens revealed over 160 distinct components, dominated by GD3 and GT1 forms. The presence of GT1c(d18:1/24:1) was identified as a potential GBM marker for the first time using high performance ion mobility separation mass spectrometry.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2021)
Article
Biochemical Research Methods
Masoumeh Dorrani, Bert C. Lynn
Summary: This study presents a lithium cationization methodology for mass spectrometry sequencing of advanced lignin oligomers with different bonding motifs. Sequence rules were proposed based on the fragment ions, and the fragmentation pathways were further confirmed using multi-stage collision-induced dissociation experiments.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2022)
Article
Biochemical Research Methods
Rebecca L. Cain, Ian K. Webb
Summary: Electrospray ionization mass spectrometry (ESI-MS) experiments were used to study the solution-like structures of intact proteins, specifically by controlling the protein unfolding process and analyzing folding intermediates. By mixing various pH solutions online with aqueous cytochrome C, the changes in charge states, arrival time distributions (ATDs), and electron capture dissociation (ECD) were measured to detect folding intermediates and unfolded protein structures.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Yun Zhu, Samantha Schrecke, Shuli Tang, Melanie T. Odenkirk, Thomas Walker, Lauren Stover, Jixing Lyu, Tianqi Zhang, David Russell, Erin S. Baker, Xin Yan, Arthur Laganowsky
Summary: This study reveals the selective modulation of phosphatidylserine (PS) binding to TRAAK by cupric ions, while TREK2 is unaffected. Other ions have no impact on the binding of both channels. Additionally, TRAAK shows stronger binding with Cu2+ and Zn2+ compared to TREK2.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Analytical
Thomas E. Walker, Arthur Laganowsky, David H. Russell
Summary: Charge reduction reactions play a crucial role in native mass spectrometry (nMS) by retaining native-like structures and noncovalent interactions of protein complexes. In this study, we provide new evidence that surface-active charge reducing reagents remove excess charge from droplets, thereby decreasing their overall charge. These processes are linked to the charge residue and ion evaporation models of electrospray ionization (ESI), and higher surface activity of amines leads to more efficient charge reduction of protein ions. Additionally, higher emitter potentials in ESI are associated with lower average charge states of protein complexes.
ANALYTICAL CHEMISTRY
(2022)
Article
Physics, Atomic, Molecular & Chemical
Syuan-Ting Kuo, Shuli Tang, David H. Russell, Xin Yan
Summary: This study reports a method for characterizing the positional and geometric isomers of phospholipids using copper (I) ion complexed with phospholipids. By applying multi-stage fragmentation and measuring collision cross sections, the method enables rapid and effective distinction of isomers in lipid samples.
INTERNATIONAL JOURNAL OF MASS SPECTROMETRY
(2022)
Article
Biochemistry & Molecular Biology
Kai S. Yang, Lauren R. Blankenship, Syuan-Ting Alex Kuo, Yan J. Sheng, Pingwei Li, Carol A. Fierke, David H. Russell, Xin Yan, Shiqing Xu, Wenshe Ray Liu
Summary: As a novel covalent modification, a Y-shaped, S-O-N-O-S-bridged post-translational cross-link connecting three residues C22, C44, and K61 in the main protease (M-Pro) of SARS-CoV-2 was frequently observed during crystallographic analyses. This cross-link potentially serves as a redox switch to regulate the catalytic activity of M-Pro, a drug target of COVID-19. Targeting the open active site formed by this linkage could be a potential strategy for the development of SARS-CoV-2 antivirals, especially in combination with other active-site-targeting molecules such as paxlovid.
ACS CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Analytical
Varun V. Gadkari, Brock R. Juliano, Christopher S. Mallis, Jody C. May, Ruwan T. Kurulugama, John C. Fjeldsted, John A. McLean, David H. Russell, Brandon T. Ruotolo
Summary: Through comparing three laboratories, the reproducibility of collision-induced unfolding (CIU) in protein studies was evaluated. The results showed that within the same laboratory, CIU fingerprints were repeatable with an RMSD value of less than 5%. The collision cross section (CCS) values of CIU intermediates were consistent across the laboratories, but the activation potentials required for protein CIU transitions varied between the three laboratories.
Article
Chemistry, Analytical
Liqi Fan, David H. Russell
Summary: Cu, a highly redox active metal, can damage DNA and other cellular components, but its adverse effects can be mitigated by metallothioneins (MT). This study used mass spectrometry techniques to investigate the structure and stability of Cu-MT complexes and compared them with Ag-MT complexes. The results showed that Cu+ ions first bind to the beta-domain and then to the alpha-domain to form different Cu-i-MT complexes.
Article
Chemistry, Analytical
Robert L. Schrader, Thomas E. Walker, Sumeet Chakravorty, Gordon A. Anderson, Peter T. A. Reilly, David H. Russell
Summary: Digital mass filters are useful for analyzing large molecules as they can isolate high-m/z ions without requiring high RF and DC voltages. The Mathieu stability diagrams show that capacitors introduce voltage offsets between quadrupole rod pairs, depending on the waveform voltage and duty cycle. This changes the ion's a value, allowing for isolation of single-charge states for protein complexes up to 800 kDa. An isolation resolving power of approximately 280 was achieved for an ion of m/z 12,315 (z = 65+) for the 800.5 kDa GroEL D398A complex, corresponding to an m/z window of 44.
ANALYTICAL CHEMISTRY
(2023)
Article
Engineering, Environmental
Dennys Leyva, Muhammad Usman Tariq, Rudolf Jaffe, Fahad Saeed, Francisco Fernandez-Lima
Summary: Dissolved Organic Matter (DOM) is a significant component of the global carbon cycle. This study used high-resolution mobility and ultrahigh-resolution Fourier transform ion cyclotron resonance tandem mass spectrometry (FT-ICR MS/MS) to compare four solid phase extracted (SPE) DOM samples from three freshwater ecosystems. Comparison of structural families revealed dissimilarities in the structural footprint of the samples. Inclusion of isomeric content in the structural family description suggested additional transformation pathways and/or source variations.
ENVIRONMENTAL SCIENCE & TECHNOLOGY
(2023)
Article
Biochemical Research Methods
Dallas P. Freitas, Xi Chen, Erin A. Hirtzel, Madison E. Edwards, Joohan Kim, Hongying Wang, Yuxiang Sun, Klaudia I. Kocurek, David Russell, Xin Yan
Summary: In this study, we developed an in situ droplet-based derivatization method for rapid analysis of tissue lipids at multiple isomer levels. The method involves on-tissue derivatization using the TriVersa NanoMate LESA pipette, followed by extraction and analysis of the derivatized lipids using chip-based LESA mass spectrometry (MS) and tandem MS. This approach enables characterization of lipid isomers at the carbon-carbon double-bond positional and sn-positional levels, as well as relative quantitation based on diagnostic ion intensities. The method allows for multiple derivatizations at different spots in the same functional region of an organ, facilitating orthogonal lipid isomer analysis using a single tissue slide. Lipid isomers in different regions of the mouse brain were profiled, demonstrating the potential of this droplet-based derivatization method in tissue lipid studies requiring fast sample-to-result turnovers.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Analytical
Miguel Santos-Fernandez, Kevin Jeanne Dit Fouque, Francisco Fernandez-Lima
Summary: There is a growing demand for cost-effective benchtop analytical instruments that can separate and characterize biological samples. In this study, a trapped ion mobility spectrometry and ultraviolet photodissociation capability were integrated into a commercial mass spectrometer, allowing for efficient analysis of complex biological samples. The platform showed great potential for the analysis of positional isomers with different PTM locations, providing effective sequence confirmation and identification of fragment ions associated with PTM.
ANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
German Mejia, Linjia Su, Popular Pandey, Kevin Jeanne Dit Fouque, Anthony J. McGoron, Francisco Fernandez-Lima, Jin He, Alexander M. Mebel, Fenfei Leng
Summary: We reported a spontaneous reaction between the anticancer drug doxorubicin and GTP or dGTP. The reaction produces a covalent product, the doxorubicin-GTP or -dGTP conjugate, which accumulates in cancer cells but cannot enter nuclei. This conjugate exhibits lower cytotoxicity compared to doxorubicin and suggests that doxorubicin may target ATP and GTP.
CHEMICAL RESEARCH IN TOXICOLOGY
(2023)
Article
Chemistry, Physical
Lucas W. Henderson, Edie M. Sharon, Amit K. S. Gautam, Adam J. Anthony, Martin F. Jarrold, David H. Russell, Andreas Matouschek, David E. Clemmer
Summary: Mass spectrometry studies show that the stability of S. cerevisiae 20S proteasome undergoes related configurations and transitions during temperature changes, possibly linked to the opening of the proteolytic core. The study indicates that the proteasome remains intact and all transitions are reversible. Three types of structures are identified based on thermodynamic analysis: energetically stabilized closed configurations, high-entropy precursor states, and open pore structures. Opening of the 20S pore in the absence of the regulatory unit involves a charge-priming process. However, only a small fraction of precursor configurations actually open to expose the catalytic cavity.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Article
Biochemical Research Methods
Robert L. Schrader, Thomas E. Walker, David H. Russell
Summary: The use of mild collisional activation has been found to remove salts and adducts from large molecules, enhancing measurement accuracy and mass resolution. Adding a short square quadrupole between the ion funnel and transmission quadrupole effectively removes adducts and improves ejection efficiency for ions with low size-to-charge ratio.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2023)
Article
Chemistry, Multidisciplinary
Thomas Walker, He Mirabel Sun, Tiffany Gunnels, Vicki Wysocki, Arthur Laganowsky, Hays Rye, David Russell
Summary: Variable-temperature electrospray ionization (vT-ESI) native mass spectrometry (nMS) is used to investigate the thermodynamics of ATP binding to the GroEL tetradecamer chaperonin complex. The study reveals strong enthalpy-entropy compensation (EEC) and variations in stepwise free energy changes, which are consistent with the established nested cooperativity model of GroEL-ATP interactions. The entropy-driven ATP binding is attributed to ligand-induced conformational changes and reorganization of water molecules within the GroEL complex.
ACS CENTRAL SCIENCE
(2023)
Article
Chemistry, Physical
Md Shofiul Alam, Dennys Leyva, Woodline Michelin, Francisco Fernandez-Lima, Jaroslava Miksovska
Summary: In this study, it was discovered that a member of the neuronal calcium sensor family, NCS1, can complex with lanthanide ions Tb3+ and Eu3+. The affinity of NCS1 for Tb3+ is significantly higher than that for Ca2+, while Eu3+ binding is weaker. The distinct binding of Tb3+ and Eu3+ to NCS1 impacts its oligomerization and affinity for the D2R peptide.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
