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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.01028

Photobinding of Triflusal to Human Serum Albumin Investigated by Fluorescence, Proteomic Analysis and Computational Studies

  • 1Polytechnic University of Valencia, Spain
  • 2Centro de Investigación en Química Biológica y Materiales Moleculares (CiQUS), Universidad de Santiago de Compostela, Spain
  • 3Instituto de Tecnología Química (ITQ), Spain

Triflusal is a platelet antiaggregant employed for the treatment and prevention of thromboembolic diseases. After administration, it is biotransformed into its active metabolite, the 2-hydroxy-4-trifluoromethylbenzoic acid (HTB). We present here an investigation on HTB photobinding to human serum albumin (HSA), the most abundant protein in plasma, using an approach that combines fluorescence, MS/MS and peptide fingerprint analysis as well as theoretical calculations (docking and molecular dynamics simulation studies). The proteomic analysis of HTB/HSA photolysates shows that HTB addition takes place at the ε-amino groups of the Lys137, Lys199, Lys205, Lys351, Lys432, Lys541, Lys545, and Lys525 residues and involves replacement of the trifluoromethyl moiety of HTB with a new amide function. Only Lys199 is located in an internal pocket of the protein and the remaining modified residues are placed in the external part. Docking and molecular dynamic simulation studies reveal that HTB supramolecular binding to HSA occurs in the “V-cleft” region and that the process is assisted by the presence of Glu/Asp residues in the neighborhood of the external Lys, in agreement with the experimentally observed modifications. In principle, photobinding can occur with other trifluoroaromatic compounds and may be responsible for the appearance of undesired photoallergic side effects.

Keywords: Triflusal Metabolite, Human serum albumin (HSA), fluorescence, Proteomic analysis, Docking and molecular dynamics, Photoallergy

Received: 10 May 2019; Accepted: 12 Aug 2019.

Edited by:

Ke-Vin Chang, National Taiwan University Hospital, Taiwan

Reviewed by:

Oksana Lockridge, University of Nebraska Medical Center, United States
Xiaoli Meng, University of Liverpool, United Kingdom  

Copyright: © 2019 Molins-Molina, Pérez-Ruiz, Lence, González-Bello, Miranda and Jiménez. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. María Consuelo Jiménez, Polytechnic University of Valencia, Valencia, 46022, Valencia, Spain,