In this paper a novel and general procedure is presented for detection of organophosphate-inhibited human butyrylcholinesterase (HuBuChE), which is based on electrospray tandem mass spectrometric analysis of phosphylated nonapeptides obtained after pepsin digestion of the enzyme. The utility of this method is exemplified by the positive analysis of serum samples from Japanese victims of the terrorist attack with sarin in the Tokyo subway in 1995.
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http://dx.doi.org/10.1021/tx0101806 | DOI Listing |
J Chromatogr B Analyt Technol Biomed Life Sci
January 2025
Department of Chemistry, Cleveland State University, Cleveland, OH 44115, USA. Electronic address:
The integrated stress response (ISR) is a cellular defense mechanism activated under stress conditions. When the ISR is activated, it slows the production of proteins, the building blocks that cells need to function. Trans-integrated stress response inhibitor (trans-ISRIB) is a compound that can reverse the effects of ISR activation, showing promise for treating neurodegenerative diseases.
View Article and Find Full Text PDFFront Immunol
January 2025
Rudolf Virchow Center, Center for Integrative and Translational Bioimaging, Julius-Maximilians-Universität of Würzburg, Würzburg, Germany.
Background: The immunopeptidome is constantly monitored by T cells to detect foreign or aberrant HLA peptides. It is highly dynamic and reflects the current cellular state, enabling the immune system to recognize abnormal cellular conditions, such as those present in cancer cells. To precisely determine how changes in cellular processes, such as those induced by drug treatment, affect the immunopeptidome, quantitative immunopeptidomics approaches are essential.
View Article and Find Full Text PDFPNAS Nexus
January 2025
Department of Refractory Viral Diseases, National Center for Global Health and Medicine Research Institute, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.
We identified a 5-fluoro-benzothiazole-containing small molecule, TKB272, through fluorine-scanning of the benzothiazole moiety, which more potently inhibits the enzymatic activity of SARS-CoV-2's main protease (M) and more effectively blocks the infectivity and replication of all SARS-CoV-2 strains examined including Omicron variants such as SARS-CoV-2 and SARS-CoV-2 than two M inhibitors: nirmatrelvir and ensitrelvir. Notably, the administration of ritonavir-boosted nirmatrelvir and ensitrelvir causes drug-drug interactions warranting cautions due to their CYP3A4 inhibition, thereby limiting their clinical utility. When orally administered, TKB272 blocked SARS-CoV-2 replication without ritonavir in B6.
View Article and Find Full Text PDFACS Omega
January 2025
Biomolecular Measurement Division, National Institute of Standards and Technology, Gaithersburg, Maryland 20899, United States.
RNA undergoes oxidatively induced damage in living organisms analogous to DNA. RNA is even more vulnerable to damage than DNA due to its greater abundance, single-strandedness, lack of repair and chromatin proteins shield, and instability, among other effects. RNA damage can adversely affect gene expression, leading to protein synthesis alterations, cell death, and other detrimental biological consequences.
View Article and Find Full Text PDFBioanalysis
January 2025
Quantitative Pharmacology, Bicycle Therapeutics, Cambridge, MA, USA.
Background: The Bicycle® toxin conjugate (BTC) zelenectide pevedotin, formerly known as BT8009, is a novel bicyclic peptide targeting the Nectin-4 tumor antigen conjugated to the cytotoxin monomethyl auristatin E (MMAE) via a valine-citrulline cleavable linker. Zelenectide pevedotin is currently being investigated in a Phase 1/2 (Duravelo-1, NCT04561362) clinical trial to determine safety and efficacy in patients with tumors associated with Nectin-4 expression. A simple regulated bioanalytical assay was developed to quantify intact zelenectide pevedotin in patient plasma samples.
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