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Polyclonal antibody-ruthenium complex interaction as nitric oxide delivery system. Especificity and citotoxic evaluation

Grant number: 09/11471-9
Support Opportunities:Scholarships in Brazil - Master
Start date: March 01, 2010
End date: February 29, 2012
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
Principal Investigator:Roberto Santana da Silva
Grantee:Loyanne Carla Barbosa Ramos
Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The nitric oxide (NO) is a biological messenger that has vital importance in many physiological trials, such as the cardiovascular control, the road signs neural and the defense against microorganisms and tumors. Beyond this, the NO is also anticancer agent what would enable the use NO delivery agent in clinical handlings. Based on biological and chemical characteristics of the NO molecule is that becomes vital the search of systems subject to liberate NO, in controlled way, in the biological systems. One of the imminent possibilities involves nitrosyl ruthenium complexes, whose strategy would be utilize compound termodinamically stable, however assets when stimulated. Aiming in utilize the antitumoral characteristics of NO that this project has been proposed with general objective to prepare species that can act like NO delivery agents by redutimetric action. The specificity of these composed will be achieved through the interaction antigen-antibody---{Ru-NO} obtained when the conjugated antibody---{Ru-NO} will go displayed in metastatic cells. In these studies will be sinthesized the species [Ru(bpy)2(dcbpy)] (dcbpy = 4,4'-dicarboxilate-2,2'-bipyridine; bpy = 2,2'-bipyridine), [Ru(bpy)(dcbpy)2], cis-[Ru(dcbpy)2Cl2] (dcbpy = 4,4'-dicarboxylic-2,2'-bipyridine), cis-[Ru(dcbpy)2NO(L)]n+ (L = chloride, pyridine, 4-picoline, 4-acetilpyridine), [Ru(terpy)(dcbpy)Cl] (terpy = terpyridine) and [Ru(terpy)(dcbpy)NO]. The complexes will be conjugated with antibody ECV polyclonal galectin-1 and evaluated by Fluorescence Spectrum. The amount of complex-antibody on the occasion of the formation of the conjugated will be stimated also by fluorescence spectroscopy. The chemical characterization and kinetic of these systems will be evaluated by spectroscopic and electrochemistry technique. Cytotoxic experiments will be driven with cells ECV304 ( cell line from human endothelium) and the cell viability evaluated through the approach MTT.

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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)
RAMOS, LOYANNE C. B.; RODRIGUES, FERNANDO P.; BIAZZOTTO, JULIANA C.; MACHADO, SERGIO DE PAULA; SLEP, LEONARDO D.; HAMBLIN, MICHAEL R.; DA SILVA, ROBERTO S.. Targeting the mitochondrial VDAC in hepatocellular carcinoma using a polyclonal antibody-conjugated to a nitrosyl ruthenium complex. JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY, v. 23, n. 6, p. 903-916, . (09/11471-9)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
RAMOS, Loyanne Carla Barbosa. Interaction polyclonal antibody-ruthenium complex such as nitric oxide release systems. Specificity and cytotoxicity measurement. 2012. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) Ribeirão Preto.