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EXCITED STATES AS PROBES TO INVESTIGATE DRUG-DNA AND DRUG-PROTEIN INTERACTIONS. PHOTOSENSITIZED PROCESSES LEADING TO DAMAGE TO BIOMOLECULES (PHOTOBIODRUG)
Date du début: 1 mars 2013, Date de fin: 28 févr. 2015 PROJET  TERMINÉ 

"Specific interactions between drugs and biomolecules are fundamental to many biological processes. It is well known that biomolecules can undergo extensive changes upon irradiation in the presence of drugs, which can behave as photosensitizers leading to adverse side-effects (e. g., to a loss of their biological function). Thus, protein-protein photocrosslinking, or drug-protein photobinding originating photoallergy, as well as DNA damage resulting in photomutagenicity and photogenotoxicity, are well known. Clearly, a precise knowledge of the active sites where drugs can interact with biomolecules and the involved reaction mechanisms would contribute to understanding the photosensitizing potential of new drug candidates. To address this issue, photophysical techniques (fluorescence and transient absorption techniques, from the femtosecond to the nanosecond time scales) will be used in order to get insight into the mechanisms involved in drug-DNA or drug-protein interactions as well as to improve the knowledge in the photochemical reaction pathways that can provoke damage to the biomolecule. To this end, model systems, whose complexity will be progressively increased, that simulate the real drug-biomolecule interactions, will be designed in order to study their photophysical properties and photochemical reactivity. Investigation on the mechanistic pathways leading to photodamage may thus contribute to the design of new therapeutic agents inducing less adverse side effects to the organism, which may have applications in pharmaceutical and skin photoprotection industries."

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