Article
Chemistry, Analytical
Brock R. Juliano, Joseph W. Keating, Brandon T. Ruotolo
Summary: Membrane proteins are challenging targets for mass spectrometry due to the need for membrane mimetics. Infrared photoactivation has emerged as an alternative to liberate membrane proteins from surfactant micelles, but its mechanism and application in native proteomics are still unknown. This study evaluates and probes infrared photoactivation for membrane protein sequencing, proteoform identification, and native proteomics applications, and reveals its ability to dissociate detergent micelles and other membrane mimetics, as well as improve sequence coverage.
ANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Analytical
Brock R. Juliano, Joseph W. Keating, Brandon T. Ruotolo
Summary: Membrane proteins are difficult to study using native top-down mass spectrometry due to the need for membrane mimetics. In this study, infrared photoactivation was explored as an alternative method for liberating membrane proteins from surfactant micelles. The results showed that infrared photoactivation can dissociate micelles composed of different detergent classes and can be extended to other membrane mimetics such as nanodiscs, liposomes, and bicelles. This technique significantly improves membrane protein sequence coverage, typically ranging from 40% to 60%.
ANALYTICAL CHEMISTRY
(2023)
Article
Biochemical Research Methods
Ines C. Santos, Michael Lanzillotti, Ignat Shilov, Maria Basanta-Sanchez, Abhishek Roushan, Rose Lawler, Wilfred Tang, Marshall Bern, Jennifer S. Brodbelt
Summary: With the development of RNA-based therapeutics, the need for analytical methods to confirm sequences and map modifications has become urgent. This study compares different mass spectrometry techniques for sequencing modified nucleic acids and finds that UV photodissociation and activated electron photodetachment dissociation are effective for characterizing modified nucleic acids. However, different modifications can affect the fragmentation pathways and sequence coverage.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2022)
Article
Chemistry, Analytical
Benqian Wei, Muhammad A. Zenaidee, Carter Lantz, Rachel R. Ogorzalek Loo, Joseph A. Loo
Summary: This study compares the fragmentation patterns of internal and terminal fragments in mass spectrometry and finds that they share similar fragmentation propensities. The formation of internal fragments can be explained by the mobile proton model, and they can combine with terminal fragments to form complementary product ions that span the entire protein sequence.
ANALYTICA CHIMICA ACTA
(2022)
Article
Chemistry, Multidisciplinary
Luis A. A. Macias, Sara P. P. Garcia, Kayla M. M. Back, Yue Wu, G. Hall Johnson, Sekar Kathiresan, Andrew M. M. Bellinger, Ellen Rohde, Michael A. A. Freitas, James A. A. Madsen
Summary: The development of CRISPR-based gene editing tools has the potential to cure genetic disorders and revolutionize treatment for common diseases. This study focuses on the importance of guide RNA, which plays a crucial role in the success of CRISPR-based medicine. Using top-down mass spectrometry, the researchers were able to accurately assess and quantify highly modified guide RNAs, as well as identify impurities and sequence variations.
ACS CENTRAL SCIENCE
(2023)
Article
Biochemical Research Methods
Sean D. Dunham, Benqian Wei, Carter Lantz, Joseph A. Loo, Jennifer S. Brodbelt
Summary: 193 nm ultraviolet photodissociation (UVPD) allows high sequence coverage for intact proteins using terminal fragments alone. Internal fragments, which are usually ignored, have the potential to improve characterization of intact proteins. However, the identification of internal fragments generated by UVPD is less reproducible compared to HCD, with an increased risk of false-positive identifications. Proton-transfer charge reduction (PTCR) reactions can enhance the identification of internal fragments. Further research is needed to develop strategies to reduce false positive identifications of UVPD internal fragments.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Chemistry, Analytical
Simon Becher, Huixin Wang, Michael G. Leeming, William A. Donald, Sven Heiles
Summary: UVPD is a powerful method in top-down proteomics, with sequence coverages exceeding those obtained with other fragmentation methods. Factors influencing protein fragmentation and sequence coverage are actively debated. The study on UVPD experiments on model proteins revealed that sequence coverage increases with higher charge states, and the presence of charge remote and charge directed fragmentation types depending on protonation sites and protein charge states.
Article
Chemistry, Analytical
Samuel A. Miller, Kevin Jeanne Dit Fouque, Eldon R. Hard, Aaron T. Balana, Desmond Kaplan, Valery G. Voinov, Mark E. Ridgeway, Melvin A. Park, Gordon A. Anderson, Matthew R. Pratt, Francisco Fernandez-Lima
Summary: This study highlights the potential of using fast and high-resolution trapped ion mobility spectrometry combined with mass spectrometry to characterize alpha-synuclein positional glycoforms, offering insights for guiding therapeutic strategies for neurodegenerative disorders.
ANALYTICAL CHEMISTRY
(2023)
Article
Polymer Science
Aditi Khot, Brett M. Savoie
Summary: This study presents a coarse-grained modeling framework flexible enough to explore the structure-function relationships of organic mixed conductors exhibiting both ionic and electronic conductivity. The model successfully replicates experimental trends and reveals the complex interplay between polymer morphology, ionic-electronic coupling, and electrolyte distribution. This framework provides validation for future applications in establishing structure-function relationships in this important material class and suggests near-term opportunities for tailoring mixed conduction via side-chain design.
Article
Chemistry, Analytical
Maciej Modzel, Daniel T. Weltz Wollenberg, Morten Beck Trelle, Martin R. Larsen, Thomas J. D. Jorgensen
Summary: UVPD can induce extensive H/D scrambling in certain fragment ion types. Dominant b/y ions are strong indicators of H/D scrambling, while short UV irradiation time and high gas pressures can help minimize it.
ANALYTICAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Tanja Habeck, Frederik Lermyte
Summary: Top-down protein mass spectrometry provides valuable insights into protein sequence and structure, allowing for precise proteoform identification and the study of protein-ligand and protein-protein interactions. This method differs from traditional bottom-up approaches by analyzing intact proteins instead of digested peptides. This review provides an overview of top-down protein mass spectrometry experiments and highlights recent applications. Various experimental designs are recommended depending on whether sequence information or structural information is prioritized, as well as considerations of solution conditions and sample complexity.
ESSAYS IN BIOCHEMISTRY
(2023)
Article
Chemistry, Analytical
Taran Driver, Vitali Averbukh, Leszek J. Frasinski, Jon P. Marangos, Marina Edelson-Averbukh
Summary: Two-dimensional partial covariance mass spectrometry (2D-PC-MS) utilizes fragment ion abundance fluctuations in tandem mass spectra to accurately identify intact protein ions, showing higher specificity and resolution compared to one-dimensional (1D) tandem mass spectrometry (MS/MS).
ANALYTICAL CHEMISTRY
(2021)
Article
Biochemical Research Methods
Kyle J. Juetten, Jennifer S. Brodbelt
Summary: The impact of supercharging on the fragmentation patterns of six proteins under denaturing conditions was investigated using five activation methods. Changes in sequence coverage, preferential cleavage sites, and fragment ion abundances were evaluated for each method. The results showed that supercharging had different effects on sequence coverage and preferential cleavage sites depending on the activation method and the protein.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2023)
Article
Biochemical Research Methods
Zach Rolfs, Lloyd M. Smith
Summary: A significant portion of unidentified fragment ion intensity in top-down proteomics is believed to come from internal fragment ions, which contain neither protein terminus. The computational complexity of internal fragment ions has historically limited their application to low-complexity samples, but the implementation of internal fragment ion functionality in MetaMorpheus allows for proteome-wide annotation of these ions, leading to disambiguation of proteoforms and increased identification accuracy. MetaMorpheus demonstrated success in disambiguating previously unclear proteoforms and improving proteoform-spectrum matches in mammalian cell lysates.
JOURNAL OF PROTEOME RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Hao Jiang, Oskar K. G. Svensson, Lili Cao, Ulf Ryde
Summary: This study investigates possible proton transfer pathways within the FeMo cluster of nitrogenase during the conversion of N2H2 to NH3. The calculations suggest that the barriers for these reactions are reasonable if the S2B ligand remains bound to the cluster, but become prohibitively high if S2B dissociates. This indicates that reversible dissociation of S2B is unlikely during the normal reaction cycle.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Physics, Atomic, Molecular & Chemical
Daniel D. Vallejo, Joseph L. Corstvet, Facundo M. Fernandez
Summary: Electrospray ionization (ESI) is a popular method for generating ions in mass spectrometry (MS). The use of triboelectric nanogenerators as power sources for ESI shows promise in improving the analytical capabilities. This review highlights the fundamentals of ESI driven by DC power supplies, the contrasting qualities to triboelectric nanogenerator power supplies, and its applications in forensics, metabolomics, and protein structure analysis.
INTERNATIONAL JOURNAL OF MASS SPECTROMETRY
(2024)
Article
Physics, Atomic, Molecular & Chemical
Florian Kluibenschedl, Anna Ploner, Christina Meisenbichler, Robert Konrat, Thomas Mueller
Summary: Mass spectrometry imaging (MSI) is a powerful analytical technique for localizing chemicals on surfaces. A new interactive approach, called interactive mass spectrometry imaging (IMSI), has been developed using a pen-like ionization interface connected to a mass spectrometer. This approach allows for real-time tracking of the pen's motion on a surface to obtain chemical data. The IMSI method was successfully tested on inkjet-printed letters and mouse brain tissue samples.
INTERNATIONAL JOURNAL OF MASS SPECTROMETRY
(2024)
Article
Physics, Atomic, Molecular & Chemical
Shubhangee S. Gaikwad, Saurabh D. Kalkate, Amruta A. Bankar, Amol S. Bansode
Summary: A stable high-performance thin layer chromatographic technique was developed and validated for estimating the content of Paracetamol and Prochlorperazine. The method was validated according to the International Conference on Harmonization requirements. The study also investigated the degradation products of the drugs.
INTERNATIONAL JOURNAL OF MASS SPECTROMETRY
(2024)
Article
Physics, Atomic, Molecular & Chemical
Ioan Marginean
Summary: In this study, a coherent classification of electrospray axial regimes is provided based on non-linear fluid dynamics. This classification includes periodic, transient/chaotic, and stationary regimes, and emphasizes the importance of spray current measurements and electrospray characteristic curves in diagnosing the operation and transitions between these regimes. The effect of the electrospray operating regime on the mass spectrometer signal is also summarized.
INTERNATIONAL JOURNAL OF MASS SPECTROMETRY
(2024)
Article
Physics, Atomic, Molecular & Chemical
Le Thao Anh Nguyen, Chris J. Bowen, Laura Burchill, Spencer J. Williams, Richard A. J. O'Hair
Summary: D-Cysteinolic acid (D-CA) is an important metabolite in the biosulfur cycle, while a structural isomer, (R)-3-amino-2-hydroxypropanesulfonate ((R)-AHPS), is less common. Through mass spectrometry and density-functional theory, this study reveals the fragmentation reactions of these two isomers and methods to distinguish them.
INTERNATIONAL JOURNAL OF MASS SPECTROMETRY
(2024)
Article
Physics, Atomic, Molecular & Chemical
Frank J. Wensink, Deepak Pradeep, P. B. Armentrout, Joost M. Bakker
Summary: Methane and cyclopropane were reacted with Ru+ ions, and the resulting products were identified and characterized using mass spectrometry, IR action spectroscopy, and density functional theory calculations.
INTERNATIONAL JOURNAL OF MASS SPECTROMETRY
(2024)