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Structure and reactivity of hemepeptides, hemeproteins and phorphyrins in homogeneous and heterogenoeus media: basic aspects and application in nanotechnology


This project encompasses the study of several aspects of the structure and reactivity of cytochrome c, HRP, microperoxidases and porphyrins in the absence and in the presence of micelles membranes and particles. This project also includes the study of the interaction and reactivity of cytochrome c with liposomes and isolated mitochondria. Thus, the present project presents two principal targets: to develop and study catalytic systems interesting for basic area and for application in nanotechnology as well as to study the mechanisms of cytochrome c interaction with biological membranes and the consequences for its function and susceptibility to damage by excited species and free radicals. To attain these objectives it will be used physical and chemical techniques and computational methods. The principal studies to attain these objectives will be: 1-The study of catalytic systems containing porphyrins as active center involving HRP, microperoxidase, and porphyrin structure and function in homogeneous medium and associated to cationic interfaces, carbon and TiO2 nanotubes and MCM-41 mesoporous silica. 2- Interaction of cytochrome c with mitochondrial model membranes and the effects on the reactivity and susceptibility of the hemeprotein to excited species and free radicals. The project will be concerned with a) The study of electrostatic and lipid extend interaction of cytochrome c sites A and L with mitochondrial membrane models containing normal lipids and lipids oxidized by free radicals and singlet oxygen. b) Effect of cytochrome c in the generation of singlet oxygen from oxidized cardiolipin: participation of Russell mechanism and energy transfer from triplet carbonyls. c) Photodynamic effect of phenothiazines on cytochrome c, free and associated to lipid membranes. 3- Evolution profile of the structural changes that allowed the participation of cytochrome c in the apoptosis, a data that is lacking in literature. Procariotic cytochrome c from Paracoccus c550, Rhodospirillum c2 e Chlorobium c555 and eucariotic cytochrome c from Euglena (protozoa), Neurospora (mushroom), Drosophila (insect), Thunnus (fish), Xenopus (anphybian), Cheloniidae (reptile), Gallus (bird) will be cloned and expressed and these samples will be microinjected in aortic smooth muscle cells to check the capacity of these cytochrome c samples to trigger apoptosis. The apoptosis will be monitored by fluorescence and confocal microscopy. According to the results it will be constructed site-specific mutant cytochromes c, to determine the structural changes in cytochrome c that were crucial for the proapoptotic activity of the protein. These studies will be complemented with the study of the ability of cytochrome c to activate caspases in extracts of smooth muscle cells by using fluorescent substrates as well as the ability to induce lisosomal leakage, an event that will be investigated by confocal microscopy. The study of the procariotic cytochrome c ability to trigger apoptosis is grounded in the fact that these cytochromes c are structurally related to eucariotic cytochromes c. Contrary to eucariotic cytochrome c, the procariotic types exhibit significant variability of sequence and size of the polypeptide chain. But, although these cytochromes c are variable they presents very similar X ray structures with aromatic amino acids in the heme crevice and clusters of lysine residues around the prostethic group site. Also, another discussion remains in the literature: the role of the redox properties of cytochrome c in the apoptosis and this topic will be investigated by microinjection technique associated to the capacity to promote phosphatidylserine externalization. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
CASTANHEIRA, BRUNA; TRINDADE, FABIANE DE JESUS; ANDRADE, LUANA DOS SANTOS; NANTES, ISELI LOURENCO; POLITI, MARIO JOSE; TRIBONI, EDUARDO REZENDE; BROCHSZTAIN, SERGIO. Dye photodegradation employing mesoporous organosilicas functionalized with 1,8-naphthalimides as heterogeneous catalysts. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY, v. 332, p. 316-325, JAN 1 2017. Web of Science Citations: 2.
FERREIRA, JULIANA C.; ICIMOTO, MARCELO Y.; MARCONDES, MARCELO F.; OLIVEIRA, VITOR; NASCIMENTO, OTACIRO R.; NANTES, ISELI L. Recycling of the High Valence States of Heme Proteins by Cysteine Residues of Thimet-Oligopeptidase. PLoS One, v. 8, n. 11 NOV 1 2013. Web of Science Citations: 2.
GOTO, LEANDRO S.; HOKKA, CARLOS O.; LIMA, JOSE F.; PRIETO, TATIANA; ARAUJO, ANA PAULA U.; NANTES, ISELI L.; NASCIMENTO, OTACIRO R. Structure and Peroxidase Activity of Ferric Streptomyces clavuligerus orf10-encoded Protein P450CLA: UV-Visible, CD, MCD and EPR Spectroscopic Characterization. Journal of the Brazilian Chemical Society, v. 23, n. 5, p. 913-920, MAY 2012. Web of Science Citations: 2.

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Filed patent(s) as a result of this research project