0000000000234562
AUTHOR
Isabel M. Morera
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 photosensit…
Photobinding of Tiaprofenic Acid and Subprofen to Proteins and Cells: A Combined Study Using Radiolabeling, Antibodies and Laser Flash Photolysis of Model Bichromophores
Drug photoallergy is a matter of current concern. It involves the formation of drug-protein photoadducts (photoantigens) 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 bichromophoric 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…
Metodología innovadora en la universidad: sus efectos sobre los procesos de aprendizaje de los estudiantes universitarios
Se pretendía evaluar el impacto de metodología centrada en el aprendizaje sobre las estrategias de aprendizaje y los enfoques de aprendizaje de un grupo de alumnos de Química, de 1º curso de Ingeniería, de la Universitat Politécnica de Valencia. Se utilizó un diseño preexperimental, con medidas de pretest y postest, tomadas mediante el cuestionario CEVEAPEU y el CPE. La muestra estaba constituida por 20 alumnos. Los métodos docentes utilizados integraban metodología expositiva, preguntas, resolución de problemas, elaboración de una monografía, exposiciones orales, prácticas de laboratorio, trabajo en grupo, tutorías en el aula y un sistema de evaluación que hacía uso de procedimientos forma…
Isolation of cross-coupling products in model studies on the photochemical modification of proteins by tiaprofenic acid
To gain insight into the chemical nature of drug-induced photoallergy, model studies have been carried out on the photochemical modification of proteins by tiaprofenic acid. Irradiation of decarboxylated tiaprofenic acid (DTPA) in the presence of p-cresol leads to C–C- and C–O-connected p-cresol “dimers”, together with DTPA hydrodimers. The p-cresol–DTPA cross-coupling product was not detected in this reaction. However, a product of this type is formed using a more hindered phenol, such as 2,6-di-tert-butylphenol. Similar results are obtained when tiaprofenic acid (TPA) or its methyl ester are used as photosensitizers. The observed formation of “dimers” can be related to protein photo-cross…
Antibodies directed to drug epitopes to investigate the structure of drug-protein photoadducts. Recognition of a common photobound substructure in tiaprofenic acid/ketoprofen cross-photoreactivity.
Drug-induced photoallergy is an immune adverse reaction to the combined effect of drugs and light. From the mechanistic point of view, it first involves covalent binding of drug to protein resulting in the formation of a photoantigen. Hence, determination of the structures of drug-protein photoadducts is of great relevance to understand the molecular basis of photoallergy and cross-immunoreactivity among drugs. Looking for new strategies to investigate the covalent photobinding of drugs to proteins, we generated highly specific antibodies to drug chemical substructures. The availability of such antibodies has allowed us to discriminate between the different modes by which tiaprofenic acid (…
Photochemical versus aluminium chloride-catalyzed fries rearrangement of aryl hydrogen succinates. synthesis of 2(3H)-furanones
The photochemical and aluminium chloride-catalyzed Fries rearrangement of a series of aryl hydrogen succinates3 a–f to the corresponding 4-oxoacids1 a–f are compared. Both approaches are complementary: the photochemical process is more general and becomes the method of choice for the succinoylation of phenols supporting alkoxy or hydroxy substituents, while the classical rearrangement is superior in the presence of alkyl or halogen substituents. These results are applied to the preparation of the 2(3H)-furanones2 a–f.