An analytical method was developed for the determination of bound residues of the nitrofuran drugs furazolidone, nitrofurazone, furaltadone, and nitrofurantoin with a sensitivity of 1 ppb in shrimp. In this procedure, shrimp tissue is prewashed with solvents followed by overnight acid hydrolysis, during which the side chains of the bound residues are released and simultaneously derivatized with 2-nitrobenzaldehyde. After liquid-liquid extraction cleanup, the derivatives are detected and quantitated using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) with an atmospheric pressure chemical ionization interface. The method was validated using control shrimp fortified with each side-chain analyte at 1, 2, and 4 ppb. Method accuracies were >80% with coefficients of variation of <20% for all four analytes. Tissues from dosed shrimp were assayed to demonstrate the effectiveness of the method for recovering bound residues of nitrofurans. In shrimp dosed with nitrofurans, nitrofurantoin exhibited the lowest level of bound residues.
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http://dx.doi.org/10.1021/jf051615o | DOI Listing |
Alzheimers Dement
December 2024
Washington University School of Medicine, St. Louis, MO, USA.
Background: Alzheimer's disease neuropathology involves the deposition in brain of aggregates enriched with microtubule-binding-region (MTBR) of tau adopting an abnormal conformation between residues 306-378 in the core of aggregates. Anti-tau drugs targeting around this domain have the potential to interfere with the cell-to-cell propagation of pathological tau. Bepranemab is a humanized monoclonal Ig4 antibody binding to tau residues 235-250.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Yonsei University, Incheon, Incheon, Korea, Republic of (South).
Background: As amyloid-β (Aβ) aggregates are considered as the biomarkers and key factors in the pathology of Alzheimer's disease, there has been extensive investigation into Aβ-targeting compounds for the development of diagnostics and drug discovery related to the disorder. However, the polymorphic and heterogenous nature of Aβ aggregates impedes the structural understanding of their structure. Consequently it is a major challenge to develop new diagnostic and therapeutic development of AD and to study the mechanism of Aβ-targeting compounds.
View Article and Find Full Text PDFJ Chem Inf Model
January 2025
Molecular Simulations and Design Group, Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstrasse 1, 39106 Magdeburg, Germany.
Cezanne-2 (Cez2) is a deubiquitinylating (DUB) enzyme involved in the regulation of ubiquitin-driven cellular signaling and selectively targets Lys11-linked polyubiquitin chains. As a representative member of the ovarian tumor (OTU) subfamily DUBs, it performs cysteine proteolytic isopeptide bond cleavage; however, its exact catalytic mechanism is not yet resolved. In this work, we used different computational approaches to get molecular insights into the Cezanne-2 catalytic mechanism.
View Article and Find Full Text PDFFertil Steril
January 2025
Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO 63104 USA. Electronic address:
Background: Thrombin prefers substrates carrying Arg at the site of cleavage (P1) because of the presence of D189 in the primary specificity (S1) pocket but can also cleave substrates carrying Phe at P1. The structural basis of this property is unknown.
Objective: Solve the X-ray structure of thrombin bound to a ligand carrying Phe at P1 and investigate the effects of replacing D189.
J Phycol
January 2025
Department of Food & Bioproduct Sciences, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Delta-6 fatty acid desaturases, which play key roles in the biosynthesis of polyunsaturated fatty acids (PUFAs), are membrane-associated enzymes that present significant challenges for isolation and purification, complicating their structural characterization. Here we report the identification and structure-function analysis of a novel Δ6 fatty acid desaturase (PmD6) from the marine alga Prorocentrum micans with substrate preference to α-linolenic acid (18:3n-3). Structural modeling revealed a mushroom-like structure of PmD6 formed by four transmembrane α-helices as a stem and three cytoplasmic domains as a cap.
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