Mechanisms of photosensitization by drugs: Involvement of tyrosines in the photomodification of proteins mediated by tiaprofenic acid in vitro.
The photosensitizing potential of drugs must be related to their photoreactivity towards the target biomolecules. In this context, a representative photosensitizing drug (tiaprofenic acid) was co-irradiated with a model protein, bovine serum albumin (BSA). This led to a significant degree of protein crosslinking and to the formation of trace amounts of drug-BSA photoadducts. Amino acid analysis of the hydrolysed (HC1) protein showed that His and Tyr undergo a dramatic decrease (approx. 90%) as a consequence of drug-mediated photodynamic processes. When the drug was irradiated in the presence of the pure amino acids, extensive phototransformation of the latter was observed. Other photosensitizing drugs gave rise to similar processes when irradiated in the presence of BSA or the isolated amino acids. In conclusion, histidine and tyrosine appear to be key sites for the photosensitized damage to proteins. Photodegradation of the isolated amino acids in vitro may be an indicator of the photosensitizing potential of drugs.
Miranda
M A
MA
Departamento de Quimica/Instituto de Tecnologia Quimica UPV-CSIC, Universidad Politécnica de Valencia Spain.
Castell
J V
JV
Sarabia
Z
Z
Hernández
D
D
Puertes
I
I
Morera
I M
IM
Gómez-Lechón
M J
MJ