A method was developed for the determination and confirmation of furazolidone, nitrofurazone, furaltadone, and nitrofurantoin as their side-chain residues in honey using liquid chromatography-tandem mass spectrometry (LC-MS/MS). An initial solid-phase extraction cleanup of the honey samples was followed by overnight hydrolysis and derivatization of the nitrofuran side-chain residues with 2-nitrobenzaldehyde. After pH adjustment and liquid-liquid extraction, the extracts were assayed by LC-MS/MS using electrospray ionization in the positive ion mode. The method was validated at concentrations ranging from 0.5 to 2.0 ppb with accuracies of 92-103% and coefficients of variation of < or =10%. The lowest calibration standard used (0.25 ppb) was defined as the limit of quantitation for all four nitrofuran side-chain residues. The extracts and standards were also used for confirmatory purposes. Honey from dosed beehives was assayed to study the stability of the nitrofuran residues and to demonstrate the effectiveness of the method.
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http://dx.doi.org/10.1021/jf0625712 | DOI Listing |
Angew Chem Int Ed Engl
January 2025
Second Military Medical University, School of Pharmacy, 325 Guohe Road, 200433, Shanghai, CHINA.
Peptide stapling techniques have historically relied on metal-catalyzed chemical reactions, with no examples using enzymes. Here, inspired by tyrosinase-mediated oxidation, we describe the efficient side-chain to side-chain coupling of p-amino phenylalanine (Z) and tyrosine (Y) amino acids using a commercially available tyrosinase. Stapling reactions between the i, i+3 to i, i+7 positions were all performed, proceeding in good conversion and under mild conditions compatible with various side chains, functional motifs and ring sizes, with the Z-Y product found to be more stable and obtained in a higher yield than the Y-Z product.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Computer Chemistry Center, Department for Chemistry and Pharmacy, Friedrich-Alexander University Erlangen Nürnberg (FAU), Nägelsbachstraße 25, 91052 Erlangen, Germany.
Carboxypeptidase is a Zn-dependent protease that specifically recognises and hydrolyses peptides with a hydrophobic side chain at the C-terminal residue. According to hydrolysis mechanisms proposed in the literature, catalysis requires a water molecule to be close to the Zn ion so as to be activated as a nucleophile. Among small molecules that resemble the slowly hydrolysed Gly-Tyr peptide, which have been previously designed as inhibitors and characterised structurally, a variant with the terminal amino acid in a D-configuration has been the most effective.
View Article and Find Full Text PDFArch Pharm (Weinheim)
January 2025
Section of Pharmaceutical and Nutraceutical Sciences, Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Sesto Fiorentino, Firenze, Italy.
2,2'-Thio-bis(4,6-dichlorophenol), namely bithionol, is a small molecule endowed with a multifaceted bioactivity. Its peculiar polychlorinated phenolic structure makes it a suitable candidate to explore its potentialities in establishing interaction patterns with enzymes of MedChem interest, such as the human carbonic anhydrase (hCA) metalloenzymes. Herein, bithionol was tested on a panel of specific hCAs through the stopped-flow technique, showing a promising micromolar inhibitory activity for the hCA II isoform.
View Article and Find Full Text PDFJ Med Chem
January 2025
Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
The development of dual prostaglandin E receptors 2/4 (EP2/EP4) antagonists represents an attractive strategy for cancer immunotherapy. Herein, a series of 4,7-dihydro-5-thieno[2,3-]pyran derivatives with potent EP2/EP4 dual antagonism were discovered by fine-tuned structural modifications. The biphenyl side chain was found to be the key pharmacophore for the transition from EP4 antagonism to EP2/EP4 dual antagonism.
View Article and Find Full Text PDFPhys Chem Chem Phys
January 2025
Department of Chemistry, University at Albany, State University of New York, 1400 Washington Ave, Albany, NY 12222, USA.
The influence of aqueous solutions of 2-(tetrafluoro(trifluoromethyl)-λ-sulfanyl-ethan-1-ol (CFSF-ethanol) and 2,2,2-trifluoroethanol (TFE) on the secondary structure of melittin was studied using circular dichroism (CD) and molecular dynamics (MD) simulations. In water, melittin transitions into a random coil. However, upon addition of even as little as 1% by volume of CFSF-ethanol, the secondary structure of melittin stabilizes as a helix.
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