Mapping a protein recognition centre with chiral photoactive ligands. An integrated approach combining photophysics, reactivity, proteomics and molecular dynamics simulation studies

Abstract

Photobinding of CPFMe to Phe68 reveals the structural details of the recognition centre of BAAG for this ligand.

Protein Binding of Lapatinib and Its N- and O-Dealkylated Metabolites Interrogated by Fluorescence, Ultrafast Spectroscopy and Molecular Dynamics Simulations

“…These calculations were performed using GOLD 5.8.1 program (CCDC, 2020) and the protein coordinates were taken from: 1) the crystal structure of HSA in complex with hemin and myristic acid (PDB entry 1O9X) (Zunszain et al, 2003); 2) the crystal structure of BSA in complex with 3,5-diiodosalicylic acid (PDB entry 4JK4, chain A) (Sekula et al, 2013); 3) the crystal structure of HAG in the unbound form (PDB entry 3KQ0) (Schonfeld et al, 2008); and 4) our previously reported homology model of BAG using the Phyre2 (Kelley et al, 2015) homology modeling web server (Limones-Herrero et al, 2017). The experimental procedure was similar to that described for: 1) 2-acetoxy-4trifluoromethylbenzoic acid (triflusal) (Molins-Molina et al, 2019) and HSA protein with the exception that the position of hemin was used to define the binding pocket, and the radius was set to 10 Å; and 2) carprofen methyl ester and the homology model of BSA (Limones-Herrero et al, 2017). The protonated forms of the ligands (secondary and primary amines) were employed.…”

Peculiarities of Electron Transfer in Chiral Linked Systems

“…No stereoselectivity was detected at early times, only after about 10 ps. The kinetics of (R,S)-FBP-Tyr was found to decay faster than its (S,S)-analogue after 10 ps; on the contrary, for the dyads with rigid bridge, the opposite behavior was observed [8]. These differences were analyzed in view of conformational peculiarities of studied systems.…”

“…ET in chiral systems is studied by the example of nonsteroidal antiinflammatory drugs (NSAIDs), medicines that demonstrate remarkable difference in enantiomers medical activity [1,4]. PET was studied by the UV irradiation of dyads including NSAIDs linked by bridges with various electron donors [5][6][7][8][9][10]. The exploration by using fluorescence and laser flash photolysis has shown that ET in dyads is stereoselective.…”

Identification of a common recognition center for a photoactive non-steroidal antiinflammatory drug in serum albumins of different species

“…This has been proven for a model system (carprofen methyl ester/bovine 1 acid glycoprotein) using a systematic approach that combines photophysics, reactivity, proteomics and molecular dynamics simulation studies. 1 The parent drug carprofen [2-(6-chloro-9H-carbazol-2yl)propanoic acid] is a non-steroidal antiinflammatory drug (NSAID) of the 2-arylpropionic acids family employed for the treatment of pain and inflammation for almost a decade in the 90's. Then, it was removed from the market for human use, and currently tablets or injections are only used for veterinary purposes.…”