Article
Toxicology
F. Femy, G. Meesemaecker, N. Belverge, C. Courageux, A. Nervo, R. Goulay, C. Reymond, F. Chantegreil, M. Madi, F. Nachon, N. Taudon, N. Jaffre
Summary: Recent events highlight the serious threat posed by organophosphorus nerve agents (OPNAs). Inhibition of cholinesterase by OPNAs leads to the accumulation of acetylcholine, causing a cholinergic crisis and potential death. Evaluating the effectiveness of new medical countermeasures against OPNAs relies on translational animal models. We have developed a swine model of percutaneous VX intoxication and a simple enzymatic method to measure plasmatic VX concentrations over time. This method shows promise for assessing the efficacy of medical countermeasures against OPNAs.
ARCHIVES OF TOXICOLOGY
(2023)
Review
Biotechnology & Applied Microbiology
Zhongdi Song, Qunfeng Zhang, Wenhui Wu, Zhongji Pu, Haoran Yu
Summary: The strategy of rational design is to predict potential mutants based on the understanding of protein structure-function relationships and introduce mutations using site-directed mutagenesis. Rational design methods are universal, fast, and have the potential for quantitative prediction of designed sequence performance. Designing enzymes with improved activity or selectivity is challenging due to the complexity of enzyme structure and limited understanding of structure-function relationships. However, with computational advancement and deeper understanding of enzyme catalysis, rational design can simplify enzyme engineering and its application is increasing.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Biochemical Research Methods
Qiao Lv, Hui-Lan Yu, Yang Yang, Fan-Hua Meng, Xian-Dong Dai, Pei-Yu Jiang, Chang-Cai Liu
Summary: In this study, an indirect competitive ELISA (icELISA) method was developed to detect OPNA exposure in serum samples. Monoclonal antibodies (mAbs) were introduced to recognize OPNA-HSA adducts at tyrosine 411 residue. The developed method showed high sensitivity and selectivity, and has the potential for point-of-care testing of OPNA intoxication.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Daniel A. S. Kitagawa, Rafael B. Rodrigues, Thiago N. Silva, Wellington dos Santos, Vinicius C. V. da Rocha, Joyce S. F. D. de Almeida, Leandro B. Bernardo, Taynara Carvalho-Silva, Cintia N. Ferreira, Angelo A. T. da Silva, Alessandro B. C. Simas, Eugenie Nepovimova, Kamil Kuca, Tanos C. C. Franca, Samir F. de A. Cavalcante
Summary: Novel isatin derivatives linked to a pyridinium 4-oxime moiety by an alkyl chain with improved calculated properties showed comparable in vitro reactivation against paraoxon- and NEMP-inhibited acetylcholinesterase, indicating their potential as promising compounds for tackling organophosphorus poisoning.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Pauline Jacquet, Benjamin Remy, Rowdy P. T. Bross, Marco van Grol, Floriane Gaucher, Eric Chabriere, Martijn C. de Koning, David Daude
Summary: Organophosphorus nerve agents (OPNAs) are highly toxic compounds inhibiting cholinergic enzymes, but they can be effectively degraded by engineered enzymes, which not only degrade insecticides and surrogates, but also real chemical warfare agents. The research demonstrates that these enzymes can quickly degrade most toxic molecules at high concentrations and efficiently decontaminate contaminated surfaces according to NATO guidelines.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Environmental Sciences
Jin Wang, Xiaogang Lu, Runli Gao, Chengxin Pei, Hongmei Wang
Summary: Detection of biomarkers in biomedical samples is crucial for the retrospective identification of exposure to Organophosphorus neurotoxic agents (OPNAs). Common biomarkers include intact agents, degradation products and protein adducts. Direct agent identification is successful in basic experimental research, while protein adducts are more suitable for retrospective identification. However, more potential biomarkers need to be discovered.
Review
Environmental Sciences
Jianxiong Chen, Zitao Guo, Yu Xin, Zhenghua Gu, Liang Zhang, Xuan Guo
Summary: Organophosphorus compounds (OPs) have been widely used in agriculture for their high insecticidal efficiency and pose a significant threat as chemical warfare agents. Excessive and unreasonable use of OPs has caused great harm to the environment and food chain. This review focuses on the properties, structure, and catalytic mechanism of various OP-degrading enzymes, as well as methods for improving their expression level, catalytic performance, and stability. The immobilization and latest applications of OP-degrading enzymes are also discussed.
SCIENCE OF THE TOTAL ENVIRONMENT
(2023)
Article
Chemistry, Analytical
James Disley, Guzman Gil-Ramirez, Peter Eaton, Jose Gonzalez-Rodriguez
Summary: A chitosan-graphite molecular imprinted polymer has been fabricated to trap and detect DMMP by measuring the change in resistance. The material showed a high trapping capacity and consistent response, making it suitable for monitoring DMMP levels.
Article
Chemistry, Analytical
James Disley, Guzman Gil-Ramirez, Peter Eaton, Jose Gonzalez-Rodriguez
Summary: A molecular imprinted polymer (MIP) made of chitosan-doped graphite has been fabricated to detect dimethyl methylphosphonate (DMMP) by measuring the change in resistance. The MIP showed a higher trapping capacity for DMMP compared to a similar non-imprinted composite. The manufacturing process was consistent and the response to DMMP was proportional to its concentration. Overall, the CG-MIC can be used as a smart material for monitoring DMMP trapping levels. Rating: 8/10.
Article
Chemistry, Multidisciplinary
Si-Jia Liu, Zhi-Han Chen, Jia-Yi Chen, Shao-Fei Ni, Yu-Chen Zhang, Feng Shi
Summary: A new class of axially chiral styrene-based thiourea tertiary amine catalysts with efficient synthetic route, multiple chiral elements, and multiple activating groups has been designed. These catalysts have proven to be efficient in enabling the cyclization reaction of 2-benzothiazolimines and homophthalic anhydrides with high yields and excellent stereoselectivities. The role of axially chiral styrene moiety in controlling reactivity and enantioselectivity has been elucidated through theoretical calculations.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Medicinal
Maria Carmina Scala, Mariangela Agamennone, Agostina Pietrantoni, Veronica Di Sarno, Alessia Bertamino, Fabiana Superti, Pietro Campiglia, Marina Sala
Summary: Influenza is a major global health issue and the rise in drug-resistant virus strains emphasizes the need for new drugs. Previous research on bovine lactoferrin and its fragments showed antiviral effects, with recent discovery of two peptides capable of inhibiting viral infection by binding with hemagglutinin.
Article
Toxicology
Lukas Gorecki, Vendula Hepnarova, Jana Zdarova Karasova, Martina Hrabinova, Charlotte Courageux, Jose Dias, Tomas Kucera, Tereza Kobrlova, Lubica Muckova, Lukas Prchal, David Malinak, Daniel Jun, Kamil Musilek, Franz Worek, Florian Nachon, Ondrej Soukup, Jan Korabecny
Summary: Novel monoquaternary reactivators developed in this study showed superior efficacy compared to clinically used standards, with broad-spectrum capability demonstrated in both in vitro and in vivo experiments. Through detailed investigation of their reactivation mechanisms, K1374 and K1375 emerged as promising candidates for further exploration as nerve agents and insecticide antidotes.
ARCHIVES OF TOXICOLOGY
(2021)
Article
Chemistry, Physical
Yu-Fei Ao, Hui-Juan Hu, Cheng-Xin Zhao, Peng Chen, Tingting Huang, Hui Chen, Qi-Qiang Wang, De-Xian Wang, Mei-Xiang Wang
Summary: This study demonstrates efficient biocatalytic desymmetrization of meso O-heterocyclic dicarboxamides for synthesizing both antipodes of functionalized cyclic motifs, with yields up to 99.5% ee. The engineered biocatalyst shows wide substrate promiscuity, high efficiency, and excellent enantioselectivity.
Article
Microbiology
Wenyu Xiang, Patrice Clemenza, Jessie Klousnitzer, Jespar Chen, Weiheng Qin, Stephanie Tristram-Nagle, Yohei Doi, Y. Peter Di, Berthony Deslouches
Summary: Antimicrobial peptides that directly disrupt bacterial membranes may overcome resistance to traditional antibiotics. A rational framework for systematically addressing this challenge was developed using novel peptides tested against antibiotic-resistant bacteria. The study selected peptides with broad-spectrum activity and low toxicity to mammalian cells, and the shortest peptide demonstrated effectiveness in killing antibiotic-resistant bacteria and protecting mice from infection.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Fang-Ying Zhu, Meng-Yu Huang, Ken Zheng, Xiao-Jian Zhang, Xue Cai, Liang-Gang Huang, Zhi-Qiang Liu, Yu-Guo Zheng
Summary: An effective evolution strategy for (R)-to-transaminase designing was presented for the synthesis of sitagliptin intermediate. The best engineered variant exhibited significantly higher activity due to enlarged and adaptive substrate pocket and tunnel. However, further modifications are needed to enhance the industrial operation stability of the (R)-transaminase.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Meeting Abstract
Cardiac & Cardiovascular Systems
M. Trattner, K. Kehe, D. Steinritz, J. Pelisek, A. Kuehnl, L. Maegdefessel
CARDIOVASCULAR RESEARCH
(2018)
Article
Chemistry, Analytical
Christopher M. Timperley, Jonathan E. Forman, Mohammad Abdollahi, Abdullah Saeed Al-Amri, Isel Pascual Alonso, Augustin Baulig, Veronica Borrett, Flerida A. Carino, Christophe Curty, David Gonzalez Berrutti, Zrinka Kovarik, Roberto Martinez-Alvarez, Robert Mikulak, Nicia Maria Fusaro Mourao, Ramasami Ponnadurai, Slawomir Neffe, Syed K. Raza, Valentin Rubaylo, Koji Takeuchi, Cheng Tang, Ferruccio Trifiro, Francois Mauritz van Straten, Paula S. Vanninen, Volodymyr Zaitsev, Farhat Waqar, Mongia Said Zina, Marc-Michael Blum, Hugh Gregg, Elena Fischer, Siqing Sun, Pei Yang
Article
Toxicology
Dirk Steinritz, Franziska Zehfuss, Bernhard Stenger, Annette Schmidt, Tanja Popp, Kai Kehe, Harald Mueckter, Horst Thiermann, Thomas Gudermann
TOXICOLOGY LETTERS
(2018)
Article
Toxicology
Simon Lang, Tanja Popp, Christian Silvester Kriegs, Annette Schmidt, Frank Balszuweit, Georg Menacher, Kai Kehe, Horst Thiermann, Thomas Gudermann, Dirk Steinritz
TOXICOLOGY LETTERS
(2018)
Article
Toxicology
Thilo Simons, Dirk Steinritz, Birgit Boelck, Annette Schmidt, Tanja Popp, Horst Thiermann, Thomas Gudermann, Wilhelm Bloch, Kai Kehe
TOXICOLOGY LETTERS
(2018)
Article
Biophysics
Noemi Colozza, Kai Kehe, Giulio Dionisi, Tanja Popp, Amelie Tsoutsoulopoulos, Dirk Steinritz, Danila Moscone, Fabiana Arduini
BIOSENSORS & BIOELECTRONICS
(2019)
Article
Biochemistry & Molecular Biology
Georg Menacher, Frank Balszuweit, Simon Lang, Horst Thiermann, Kai Kehe, Thomas Gudermann, Annette Schmidt, Dirk Steinritz, Tanja Popp
CHEMICO-BIOLOGICAL INTERACTIONS
(2019)
Article
Toxicology
Simon Wagner, Simon Lang, Tanja Popp, Annette Schmidt, Horst Thiermann, Dirk Steinritz, Kai Kehe
TOXICOLOGY LETTERS
(2019)
Article
Health Care Sciences & Services
Kai Kehe, Roland Girgensohn, Walter Swoboda, Dan Bieler, Axel Franke, Matthias Helm, Martin Kulla, Kerstin Luepke, Thomas Morwinsky, Markus Blaetzinger, Katalyn Rossmann
JMIR MHEALTH AND UHEALTH
(2019)
Article
Toxicology
Dirk Steinritz, Simon Lang, Tanja Popp, Markus Siegert, Simone Rothmiller, Andreas Kranawetvogl, Annette Schmidt, Harald John, Thomas Gudermann, Horst Thiermann, Kai Kehe
TOXICOLOGY LETTERS
(2019)
Article
Biochemical Research Methods
Marc-Michael Blum, Annika Richter, Markus Siegert, Horst Thiermann, Harald John
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2020)
Letter
Computer Science, Artificial Intelligence
Marc-Michael Blum
NATURE MACHINE INTELLIGENCE
(2022)
Meeting Abstract
Pharmacology & Pharmacy
S. Lang, M. Siegert, T. Popp, K. Kehe, H. Thiermann, D. Steinritz
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2019)
Meeting Abstract
Chemistry, Multidisciplinary
Marc-Michael Blum
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
(2018)
Meeting Abstract
Pharmacology & Pharmacy
S. Wagner, S. Lang, T. Popp, A. Schmidt, K. Kehe, H. Thiermann, D. Steinritz
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2018)