Sources, targets and biological responses of triplet species and singlet oxygen: pathogenicity and quenching

Abstract

Through thematic project "Electronic chemiexcitation in biological systems: bioluminescence and 'photo'chemistry in the dark" granted by FAPESP under case number 2017/22501-2 to the Fungi Bioluminescence Laboratory (LBF) of the Chemistry Institute/University of São Paulo (IQ-USP), two postdoctoral fellowships were offered to candidates with PhD degree. This subproject is intended to fill one of the vacancies available for the postdoctoral internship, which will cover the goals 1, 3 and 4 of the thematic project. In a global overview of the objectives pursued during the elaboration of the project, the objective is to investigate the mechanisms of radical or enzymatic generation of electron-chemiexcited species in biological systems involved in damage of proteins and DNA thereby triggering pathogenic responses. These include: (i) mutagenic cyclobutane dimerization of DNA pyrimidines in the absence of light and their suppression by sorbates; (ii) modification of hemeproteins (HRP, myoglobin, hemoglobin) in the presence of H2O2, loss of peroxidase activity; (iii) search for new sources of singlet oxygen, specifically acrolein, present in thermoprocessor foods, and formylhydrazine, found in some toxic mushroom species (eg, Gyromitra esculenta); and (iv) enzymatic generation of triplet carbonyl products in model oxidative and carbonyl stress systems. Kinetic and spectroscopic studies, isotopic labeling and photochemical and photophysical methods will be used as experimental approaches for the development of this project. The main objective and great motivation of this project is to accumulate knowledge in the field of electronic chemiexcitation in biomedicine, in addition to developing bioanalytical tools and promoting international collaborations. (AU)