Article
Multidisciplinary Sciences
Dante Johnson, Benjamin Punshon-Smith, Jessica A. Espino, Anne Gershenson, Lisa M. Jones
Summary: Fast Photochemical Oxidation of proteins (FPOP) coupled with mass spectrometry (MS) is a valuable tool in structural proteomics. Recent advancements have expanded its applications to live cell cultures, allowing for quicker experiments and research on cellular mechanisms. The new IC-FPOP platform facilitates time-resolved experiments and automation for increased efficiency.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2021)
Review
Pharmacology & Pharmacy
Guodong Chen, Li Tao, Zhengjian Li
Summary: Molecular characterization of higher order structure in protein therapeutics is essential for various aspects in drug discovery and development. Recent advances in mass spectrometry offer orthogonal ways to characterize this structure and can be utilized for epitope mapping, aggregation assessment, and comparability studies. Future trends in applying these MS methods to HOS characterization are also discussed.
DRUG DISCOVERY TODAY
(2022)
Article
Biochemistry & Molecular Biology
Michiko Tajiri, Hiroto Aoki, Atsuko Shintani, Kaori Sue, Satoko Akashi, Yoshiaki Furukawa
Summary: Cu/Zn-superoxide dismutase (SOD1) can bind a non-stoichiometric amount of copper and zinc ions, forming a homodimer with a stochastic combination of subunits. Correct metallation of SOD1 is important for amyotrophic lateral sclerosis.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Medicine, Research & Experimental
Elizabeth Sara Hecht, Shrenik Mehta, Aaron T. Wecksler, Ben Aguilar, Nathaniel Swanson, Wilson Phung, Ananya Dubey Kelsoe, W. Henry Benner, Devin Tesar, Robert F. Kelley, Wendy Sandoval, Alavattam Sreedhara
Summary: This study investigates the binding mechanism between lipase and monoclonal antibodies, finding that the CH1 domain and lipase glycosylation play a role in mediating the binding process. The structural insights gained offer new approaches for reducing host cell protein impurity levels.
Article
Chemistry, Multidisciplinary
Kyoungmun Lee, Hyun-Ro Lee, Young Hun Kim, Jaemin Park, Suchan Cho, Sheng Li, Myungeun Seo, Siyoung Q. Choi
Summary: This study demonstrated the continuous generation of hydroxyl radicals in oil-confined aqueous microdroplets, enabling the synthesis of polymers at high reactant concentrations. The transport of hydroxyl radicals also facilitated polymerization reactions in the continuous oil phase. This interfacial phenomenon was successfully applied to the chain extension of polymers.
ACS CENTRAL SCIENCE
(2022)
Article
Chemistry, Analytical
Kenneth W. Lee, Trenton M. Peters-Clarke, Keaton L. Mertz, Graeme C. McAlister, John E. P. Syka, Michael S. Westphall, Joshua J. Coon
Summary: Isobaric tagging enables the determination of peptide sequences and relative amounts in biological samples. However, limited generation of reporter ions and unintended fragmentation can affect quantitative accuracy. In this study, we used infrared photon activation and ion parking to increase reporter ion yield. Additionally, we showed that using infrared multiphoton dissociation to generate reporter ions from multiple synchronously isolated peptide product ions significantly enhances sensitivity and dynamic range of quantitation via isobaric tagging.
ANALYTICAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Nuri Gueven, Pranathi Ravishankar, Rajaraman Eri, Emma Rybalka
Summary: Idebenone is widely described as an antioxidant drug, but there is a significant discrepancy between its pharmacokinetics and achievable tissue levels in target tissues, casting doubt on our current understanding. A new framework has been proposed based on recent discoveries to explain its mode of action, providing a rational approach for testing its effects in novel indications.
Article
Biochemical Research Methods
Owen Cornwell, James R. Ault, Nicholas J. Bond, Sheena E. Radford, Alison E. Ashcroft
Summary: The study used protein footprinting methods, HDX and FPOP, along with ion mobility-mass spectrometry to probe the conformational dynamics of beta(2)-microglobulin and its D76N variant. The results show a significant difference in HDX protection in the E-F loop region of the variant protein, indicating a perturbation in the hydrogen-bonding network. Minimal differences were observed in oxidation levels between the two proteins in the same region, suggesting modest side-chain movements.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2021)
Article
Chemistry, Analytical
Zhi Cheng, Sandeep K. Misra, Anter Shami, Joshua S. Sharp
Summary: Protein posttranslational modifications (PTMs) are crucial for regulating protein structure and function. This study utilized the IEX LC-FOX technique to investigate the structural changes of ovalbumin (OVA) during dephosphorylation. The results demonstrated the utility of IEX LC-FOX for analyzing PTMs in dynamic systems.
ANALYTICAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Hsin-Chieh Yang, Weikai Li, Jie Sun, Michael L. Gross
Summary: Understanding the higher-order structure of membrane proteins is crucial for comprehending their function. Recent advances in mass spectrometry have provided opportunities in resolving the dynamics and structures of membrane proteins. This review article discusses the challenges and achievements in using mass spectrometry techniques, including hydrogen deuterium exchange, native mass spectrometry, and footprinting methods.
Article
Polymer Science
Fanfan Li, Yi Yu, Hanyu Lv, Guiting Cai, Yanwu Zhang
Summary: Twisted ZnTHP-Me2Si and layered ZnTHP-Ph2Si, synthesized by cross-linking ZnTHP, show high active site loadings and are effective photocatalysts for the polymerization of NIPAm. Twisted ZnTHP-Me2Si, with a larger surface area and more uniform pore distribution, accelerates the polymerization reaction more effectively.
Article
Chemistry, Multidisciplinary
Lingqi Qiu, R. Graham Cooks
Summary: Microdroplets exhibit unique chemistry, including simultaneous oxidation and reduction reactions. The active reagent is identified as the water radical cation/anion pair. The coexistence of oxidative and reductive species supports the existence of a double-layer structure at the microdroplet surface.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Karen E. Butler, Yoshihiko Takinami, Adam Rainczuk, Erin S. Baker, Blaine R. Roberts
Summary: Native mass spectrometry combined with IMS-MS technology can be used to study the tertiary and quaternary structure of proteins, validate other structural determination methods, and provide more comprehensive structural information.
FRONTIERS IN CHEMISTRY
(2021)
Article
Chemistry, Physical
Endre-Zsolt Kedves, Claudiu Fodor, Akos Fazekas, Istvan Szekely, Akos Szamosvolgyi, Andras Sapi, Zoltan Konya, Lucian Cristian Pop, Lucian Baia, Zsolt Pap
Summary: This study showed that MoO3 can effectively inhibit the rate of Fenton reactions, thus reducing the decomposition of organic compounds, which might be due to the scavenging effect of MoO3 on OH radicals. The results also demonstrated that the inhibition efficiency of MoO3 is strongly correlated with the acidification rate of the solution.
APPLIED SURFACE SCIENCE
(2023)
Article
Chemistry, Multidisciplinary
Jun Hu, Ting Wang, Wen-Jun Zhang, Han Hao, Qiao Yu, Hang Gao, Nan Zhang, Yun Chen, Xing-Hua Xia, Hong-Yuan Chen, Jing-Juan Xu
Summary: A novel mass spectrometric method was developed to probe the flash chemistry of electrogenerated reactive intermediates through rapid collision mixing of electrosprayed microdroplets. This method allows for fast identification and exploration of ultrafast initial transformations in the reaction process.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemical Research Methods
Hanliu Wang, Joseph Eschweiler, Weidong Cui, Hao Zhang, Carl Frieden, Brandon T. Ruotolo, Michael L. Gross
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2019)
Article
Medicine, Research & Experimental
Mingyan Cao, Niluka De Mel, Anthony Shannon, Meagan Prophet, Chunlei Wang, Weichen Xu, Ben Niu, Jun Kim, Methal Albarghouthi, Dengfeng Liu, Eric Meinke, Shihua Lin, Xiangyang Wang, Jihong Wang
Article
Chemistry, Medicinal
Mingyan Cao, Weichen Xu, Ben Niu, Ivy Kabundi, Haibin Luo, Meagan Prophet, Weimin Chen, Dengfeng Liu, Sergei Saveliev, Marjeta Urh, Jihong Wang
JOURNAL OF PHARMACEUTICAL SCIENCES
(2019)
Article
Medicine, Research & Experimental
Brian C. Mackness, Julie A. Jaworski, Ekaterina Boudanova, Anna Park, Delphine Valente, Christine Mauriac, Olivier Pasquier, Thorsten Schmidt, Mostafa Kabiri, Abdullah Kandira, Katarina Radosevic, Huawei Qiu
Article
Biochemistry & Molecular Biology
Ben Niu, Todd C. Appleby, Ruth Wang, Mariya Morar, Johannes Voight, Armando G. Villasenor, Sheila Clancy, Sarah Wise, Jean-Philippe Belzile, Giuseppe Papalia, Melanie Wong, Katherine M. Brendza, Latesh Lad, Michael L. Gross
Article
Multidisciplinary Sciences
Ben Niu, Michael Martinelli II, Yang Jiao, Chunlei Wang, Mingyan Cao, Jihong Wang, Eric Meinke
Article
Biochemistry & Molecular Biology
Ben Niu, Brian C. Mackness, Jill A. Zitzewitz, C. Robert Matthews, Michael L. Gross
Article
Multidisciplinary Sciences
Que N. Van, Cesar A. Lopez, Marco Tonelli, Troy Taylor, Ben Niu, Christopher B. Stanley, Debsindhu Bhowmik, Timothy H. Tran, Peter H. Frank, Simon Messing, Patrick Alexander, Daniel Scott, Xiaoying Ye, Matt Drew, Oleg Chertov, Mathias Losche, Arvind Ramanathan, Michael L. Gross, Nicolas W. Hengartner, William M. Westler, John L. Markley, Dhirendra K. Simanshu, Dwight Nissley, William K. Gillette, Dominic Esposito, Frank McCormick, S. Gnanakaran, Frank Heinrich, Andrew G. Stephen
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Biochemical Research Methods
Trina Mouchahoir, John E. Schiel, Rich Rogers, Alan Heckert, Benjamin J. Place, Aaron Ammerman, Xiaoxiao Li, Tom Robinson, Brian Schmidt, Chris M. Chumsae, Xinbi Li, Anton Manuilov, Bo Yan, Gregory O. Staples, Da Ren, Alexander J. Veach, Dongdong Wang, Wael Yared, Zoran Sosic, Yan Wang, Li Zang, Anthony M. Leone, Peiran Liu, Richard Ludwig, Li Tao, Wei Wu, Ahmet Cansizoglu, Andrew Hanneman, Greg W. Adams, Irina Perdivara, Hunter Walker, Margo Wilson, Arnd Brandenburg, Nick DeGraan-Weber, Stefano Gotta, Joe Shambaugh, Melissa Alvarez, X. Christopher Yu, Li Cao, Chun Shao, Andrew Mahan, Hirsh Nanda, Kristen Nields, Nancy Nightlinger, Helena Maria Barysz, Michael Jahn, Ben Niu, Jihong Wang, Gabriella Leo, Nunzio Sepe, Yan-Hui Liu, Bhumit A. Patel, Douglas Richardson, Yi Wang, Daniela Tizabi, Oleg Borisov, Yali Lu, Ernest L. Maynard, Albrecht Gruhler, Kim F. Haselmann, Thomas N. Krogh, Carsten P. Sonksen, Simon Letarte, Sean Shen, Kristin Boggio, Keith Johnson, Wenqin Ni, Himakshi Patel, David Ripley, Jason C. Rouse, Ying Zhang, Carly Daniels, Andrew Dawdy, Olga Friese, Thomas W. Powers, Justin B. Sperry, Josh Woods, Eric Carlson, K. Ilker Sen, St John Skilton, Michelle Busch, Anders Lund, Martha Stapels, Xu Guo, Sibylle Heidelberger, Harini Kaluarachchi, Sean McCarthy, John Kim, Jing Zhen, Ying Zhou, Sarah Rogstad, Xiaoshi Wang, Jing Fang, Weibin Chen, Ying Qing Yu, John G. Hoogerheide, Rebecca Scott, Hua Yuan
Summary: The MAM Consortium conducted an interlaboratory study to evaluate NPD performance across the industry, with results showing representative high-resolution MS capabilities. Critical elements of NPD were identified to further refine the methodology and speed up adoption into manufacturer-specific protein therapeutic product life cycles.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2021)
Article
Chemistry, Analytical
Chen Qian, Ben Niu, Rod Brian Jimenez, Jihong Wang, Methal Albarghouthi
Summary: The multi-attribute method based on liquid chromatography-tandem mass spectrometry is a powerful tool for monitoring multiple product quality attributes simultaneously, and a need for a universal and high-throughput workflow has been identified to better implement this method. Manual sample preparation for MAM is labor intensive and produces variations, therefore a fully automated peptide mapping procedure has been developed to improve sample handling capacity and outcome reproducibility.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2021)
Article
Biochemical Research Methods
Lucas K. Kimerer, Ben Niu, Timothy M. Pabst, Weiguo Zhai, Alan K. Hunter, Giorgio Carta
Summary: The study on elution and adsorptive behavior of a bivalent bispecific antibody and associated fragments on two cation exchange chromatography media revealed that configurational flexibility affects multi-peak elution behavior, while mass transfer limitations lead to broader peaks that obscure the multi-peak elution behavior.
JOURNAL OF CHROMATOGRAPHY A
(2021)
Article
Biotechnology & Applied Microbiology
Siddharth S. Parasnavis, Ben Niu, Matthew Aspelund, Wai K. Chung, Mark Snyder, Steven M. Cramer
Summary: A systematic workflow was developed to investigate selectivity differences and preferred binding patches for bispecific monoclonal antibodies and their parental antibodies on multimodal cation exchange resin systems. Chromatographic screening, surface property mapping, and protein footprinting were utilized to analyze the interactions of intact antibodies and fragments, revealing that interactions with the resins were primarily driven by the Fab fragments. The study provides insights into the chromatographic selectivity of large multidomain molecules and can contribute to improved biomanufacturability and downstream bioprocess development.
BIOTECHNOLOGY AND BIOENGINEERING
(2022)
Article
Biochemical Research Methods
Ben Niu, Michael Martinelli, Niluka de Mel, Eric Meinke, Weiguo Zhai, Greg Kilby, Wei Xu, Xiaoyu Chen, Chunlei Wang
Summary: Therapeutic monoclonal antibodies (mAbs) are heterogeneous and require a variety of separation methods for study and control. Protein oxidation introduced during fractionation may complicate data interpretation, with higher-energy detectors and lower fraction concentrations exacerbating the issue. Solutions with oxidation scavengers can effectively eliminate oxidation artifacts and improve peak assignment accuracy.
JOURNAL OF CHROMATOGRAPHY A
(2022)
Article
Medicine, Research & Experimental
Ruijun Zhang, Ponraj Prabakaran, Xiaocong Yu, Brian C. Mackness, Ekaterina Boudanova, Joern Hopke, Jose Sancho, Jacqueline Saleh, HyunSuk Cho, Ningning Zhang, Helene Simonds-Mannes, Samuel D. Stimple, Dietmar Hoffmann, Anna Park, Partha S. Chowdhury, Sambasiva P. Rao
Summary: This study presents a process to rapidly identify and express antibodies for functional characterization, using two approaches to isolate antibodies to five different targets. The high throughput functional screening allowed the rapid identification of several functional antibodies, demonstrating the potential of the plasmid-free system for deep functional screening during antibody discovery.
Article
Medicine, Research & Experimental
Delphine Valente, Christine Mauriac, Thorsten Schmidt, Ingo Focken, Jochen Beninga, Brian Mackness, Huawei Qiu, Pascale Vicat, Abdullah Kandira, Katarina Radosevic, Srini Rao, John Darbyshire, Mostafa Kabiri