Drug-photosensitized protein modification: identification of the reactive sites and elucidation of the reaction mechanisms with tiaprofenic acid/albumin as model system.
Certain drugs can photosensitive the formation of protein modifications, which are thought to be responsible for the occurrence of photoallergy. In the present work, the UV irradiation of serum albumin in the presence of tiaprofenic acid has been studied as a model system for drug-photosensitized protein modifications. The photolysates evidenced that His, Tyr, and Trp are the reactive sites of the protein. The experimental results strongly suggest that formal hydrogen abstraction from the OH or NH groups of Tyr or Trp by the excited drug is the key photochemical process. Competition between cage escape and in cage recombination of the resulting radical pairs governs the final outcome: protein photo-cross-linking versus drug-protein adduct formation. These findings are highly relevant to understand the process of photohapten formation, the first event in the onset of photoallergy.
Miranda
M A
MA
Departamento de Química/Instituto de Tecnología Química UPV-CSIC, Universidad Politécnica de Valencia, Spain.
Castell
J V
JV
Hernández
D
D
Gómez-Lechón
M J
MJ
Bosca
F
F
Morera
I M
IM
Sarabia
Z
Z
D000596:Amino Acids / Q000737:chemistry; D003408:Cresols / Q000737:chemistry; D003432:Cross-Linking Reagents; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D004369:Pentetic Acid / Q000737:chemistry; D010777:Photochemistry; D017319:Photosensitizing Agents / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D011422:Propionates / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D012709:Serum Albumin / Q000737:chemistry / Q000187:drug effects*
D000596:Amino Acids; D003408:Cresols; D003432:Cross-Linking Reagents; D017319:Photosensitizing Agents; D011422:Propionates; D012709:Serum Albumin; C021270:tiaprofenic acid; C032538:4-cresol; D004369:Pentetic Acid