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Article

Fluorine-Containing Drug Administration in Rats Results in Fluorination of Selected Proteins in Liver and Brain Tissue

1
Biological and Chemical Research Centre, Faculty of Chemistry, University of Warsaw, Zwirki i Wigury 101, 02-089 Warsaw, Poland
2
Center for Translational Medicine, Warsaw University of Life Science, Nowoursynowska 100, 02-797 Warsaw, Poland
3
Department of Immunology, Transplantology and Internal Diseases, Medical University of Warsaw, Nowogrodzka 59, 02-006 Warsaw, Poland
4
Department of Bioinformatics, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5a, 02-106 Warsaw, Poland
5
Department of Clinical Nursing, Medical University of Warsaw, Ciolka Street 27, 01-445 Warsaw, Poland
*
Author to whom correspondence should be addressed.
Academic Editor: Prasanth Puthanveetil
Int. J. Mol. Sci. 2022, 23(8), 4202; https://doi.org/10.3390/ijms23084202
Received: 5 March 2022 / Revised: 31 March 2022 / Accepted: 9 April 2022 / Published: 11 April 2022
(This article belongs to the Section Molecular Pharmacology)
In many pharmaceuticals, a hydrogen atom or hydroxyl group is replaced by a fluorine to increase bioavailability and biostability. The fate of fluorine released from fluorine-containing drugs is not well investigated. The aim of this study was to examine possible fluorination of proteins in rat liver and brain after administration of the fluorinated drug cinacalcet. We assigned 18 Wistar rats to a control group (n = 6) and a group treated with cinacalcet (2 mg kg−1/body weight, 5 days/week), divided into 7 day (n = 6) and 21 day (n = 6) treatment subgroups. Fluorinated proteins were identified using a free proteomics approach; chromatographic separation and analysis by high-resolution mass spectrometry; peptide/protein identification using the Mascot search algorithm; manual verification of an experimentally generated MS/MS spectrum with the theoretical MS/MS spectrum of identified fluorinated peptides. Three fluorinated proteins (spectrin beta chain; carbamoyl-phosphate synthase [ammonia], mitochondrial; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1) were identified in the liver and four (spectrin beta chain, dihydropyrimidinase-related protein 4, prominin-2, dihydropyrimidinase-related protein 4) in the brain tissue after 21 days of cinacalcet treatment, but not in the control group. Introduction of fluorine into an organism by administration of fluorinated drugs results in tissue-specific fluorination of proteins. View Full-Text
Keywords: fluorinated drug; protein fluorination; drug biotransformation; fluorine fluorinated drug; protein fluorination; drug biotransformation; fluorine
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MDPI and ACS Style

Gawor, A.; Gajewski, Z.; Paczek, L.; Czarkowska-Paczek, B.; Konopka, A.; Wryk, G.; Bulska, E. Fluorine-Containing Drug Administration in Rats Results in Fluorination of Selected Proteins in Liver and Brain Tissue. Int. J. Mol. Sci. 2022, 23, 4202. https://doi.org/10.3390/ijms23084202

AMA Style

Gawor A, Gajewski Z, Paczek L, Czarkowska-Paczek B, Konopka A, Wryk G, Bulska E. Fluorine-Containing Drug Administration in Rats Results in Fluorination of Selected Proteins in Liver and Brain Tissue. International Journal of Molecular Sciences. 2022; 23(8):4202. https://doi.org/10.3390/ijms23084202

Chicago/Turabian Style

Gawor, Andrzej, Zdzislaw Gajewski, Leszek Paczek, Bozena Czarkowska-Paczek, Anna Konopka, Grzegorz Wryk, and Ewa Bulska. 2022. "Fluorine-Containing Drug Administration in Rats Results in Fluorination of Selected Proteins in Liver and Brain Tissue" International Journal of Molecular Sciences 23, no. 8: 4202. https://doi.org/10.3390/ijms23084202

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