Estudo espectroscópico da interação entre as proteínas séricas humanas Albumina e transferrina com o potencial agente quimioterapêutico cloreto de cis-tetraminodiclorutênio (III)
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2013-09-13
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Universidade Federal de Goiás
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Motivated by the perspective of ruthenium complexes to be used in cancer treatment,
our research group has tested the hipotesis that some complexes of Ru (III) are able
to interact with serum proteins, particularly albumin and transferrin. The Complex cis-
[RuCl2(NH3)4]Cl (CTRu(III)) have been tested against different kind of tumor cells,
obtaining good results. Starting from promising results obtained with this compound,
subsequent studies are required to understanding the mechanism by which it exerts
specificity for tumor cells. In this article, we report the first application of absorption
UV-Vis, Fluorescence and Electron Paramagnetic Resonance (EPR) spectroscopy,
to study the complex CTRu(III) interaction with human serum albumin (hsA) and
bovine serum albumin (bsA). Fluorescence measurements revealed strong proteinsbound
complex with Ksv of 1.32 x 105 and 3.71 x 105 for hsA and bsA, respectively.
EPR spectra from mono-nuclear Ru(III) complexes in buffer, showed a significant
decrease in the overall signal intensity following the first aquation step, is consistent
with the formation of oxo-bridged Ru(III) dimers. EPR spectra revealed that the BSA
very rapid binding to the protein via covalent binding through ligand-exchange with
protein side chains, likely with histidine imidazoles. On the other hand, the complex
binds non-covalently in hsA, probably as a product of the oligomerization of the
complex in hemin-biding pocket. Furthermore, two species are slowly formed by
covalent binding of the complex with the histidine residues, producing a species of
axial symmetry and the other rhombic symmetry. These bonds seem to arise from
the interaction of the complex with the histidine residue located in the binding
Sudlow’s site II.
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GUEDES, Adriana Pereira Mundim. Estudo espectroscópico da interação entre as proteínas séricas humanas Albumina e transferrina com o potencial agente quimioterapêutico cloreto de cis-tetraminodiclorutênio (III). 2013. 79 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia, 2013.