Photobinding of Tiaprofenic Acid and Suprofen to Proteins and Cells: A Combined Study Using Radiolabeling, Antibodies and Laser Flash Photolysis of Model Bichromophores

Abstract

Abstract Drug photoallergy is a matter of current concern. It involves the formation of drug‐protein photoadducts (pho‐toantigens) that may ultimately trigger an immunological response. Tyrosine residues appear to be key binding sites in proteins. The present work has investigated the photobinding of tiaprofenic and (TPA) and the closely related isomer suprofen (SUP) to proteins and cells by means of radioactive labeling and drug‐directed antibodies. To ascertain whether preassociation with the protein may play a role in photoreactivity, two model bichro‐mophoric compounds (TPA‐Tyr and SUP‐Tyr) have been prepared and studied by laser flash photolysis. The results of this work show that (a) TPA and SUP photo‐bind to proteins with similar efficiencies, (b) both drugs form photoadducts that share a basic common structure, as they are recognized by the same antibody and (c) drug‐protein preassociation must play a key role in photoreactivity, as indicated by the dramatic decrease in the triplet state lifetimes of the model bichromophores compared to the parent drugs.