RT Journal Article
T1 Photobinding of triflusal to human serum albumin investigated by fluorescence, proteomic analysis, and computational studies
A1 Molins Molina, Oscar
A1 Pérez Ruiz, Raúl
A1 Lence Quintana, Emilio José
A1 González Bello, Concepción
A1 Miranda, Miguel A.
A1 Jiménez, Consuelo M.
K1 Triflusal metabolite
K1 Human serum albumin
K1 Fluorescence
K1 Proteomic analysis
K1 Docking and molecular dynamics
AB Triflusal is a platelet antiaggregant employed for the treatment and prevention ofthromboembolic diseases. After administration, it is biotransformed into its activemetabolite, the 2-hydroxy-4-trifluoromethylbenzoic acid (HTB). We present here aninvestigation on HTB photobinding to human serum albumin (HSA), the most abundantprotein in plasma, using an approach that combines fluorescence, MS/MS, andpeptide fingerprint analysis as well as theoretical calculations (docking and moleculardynamics simulation studies). The proteomic analysis of HTB/HSA photolysates showsthat HTB addition takes place at the ε-amino groups of the Lys137, Lys199, Lys205,Lys351, Lys432, Lys525, Lys541 and Lys545 residues and involves replacement ofthe trifluoromethyl moiety of HTB with a new amide function. Only Lys199 is locatedin an internal pocket of the protein, and the remaining modified residues are placed inthe external part. Docking and molecular dynamic simulation studies reveal that HTBsupramolecular binding to HSA occurs in the “V-cleft” region and that the process isassisted by the presence of Glu/Asp residues in the neighborhood of the external Lys,in agreement with the experimentally observed modifications. In principle, photobindingcan occur with other trifluoroaromatic compounds and may be responsible for theappearance of undesired photoallergic side effects
PB Frontiers Media
YR 2019
FD 2019
LK http://hdl.handle.net/10347/21313
UL http://hdl.handle.net/10347/21313
LA eng
NO Molins-Molina O, Pérez-Ruiz R, Lence E, González-Bello C, Miranda MA. and Jiménez M.C (2019) Photobinding of Triflusal to Human Serum Albumin Investigated by Fluorescence, Proteomic Analysis, and Computational Studies. Front. Pharmacol. 10:1028. doi: 10.3389/fphar.2019.01028
NO We gratefully acknowledge financial support from the SpanishGovernment (CTQ2016-78875-P, SAF2016-75638-R, BES-2014-069404, and RETICS network ARADyAL RD16/0006/0030),the Generalitat Valenciana (PROMETEO/2017/075 andCIDEGENT/2018/044), the Xunta de Galicia [Centro Singular deInvestigación de Galicia accreditation 2016–2019 (ED431G/09),ED431B 2018/04 and post-doctoral fellowship to EL], and theEuropean Union (European Regional Development Fund—ERDF). The proteomic analysis was performed in the proteomicsfacility of SCSIE University of Valencia that belongs to ProteoRedPRB3 and is supported by grant PT17/0019, of the PE I+D+i2013–2016, funded by ISCIII and ERDF. We are grateful to theCentro de Supercomputación de Galicia (CESGA) for use of theFinis Terrae computer
DS Minerva
RD 22 abr 2026