Publication Type Journal Article
Title Evaluation of the binding of four anti-tumor Casiopeinas to human serum albumin
Authors Isabel Correia Sladjana Borovic Isabel Cavaco Cristina P. Matos Somnath Roy Hugo M. Santos Luz Fernandes Jose L. Capelo Lena Ruiz-Azuara J.C. Pessoa
Groups BIOIN
Journal JOURNAL OF INORGANIC BIOCHEMISTRY
Year 2017
Month October
Volume 175
Number
Pages 284-297
Abstract The metal complexes designated by Casiopeinas (R) are mixed-ligand Cu-II-compounds some of them having promising antineoplastic properties. We report studies of binding of Cu(glycinato)(4,7-dimethyl-1,10-phenanthroline) (Cas-II-Gly (1)), Cu(acetylacetonato)(4,7-dimethy1-1,10-phenanthroline) (Cas-III-Ea (2)), Cu(glycinato) (4,4 -dimethyl-2,2 -bipyridine) (Cas-W-Gly (3)) and Cu(acetylacetonato)(4,4 -dimethyl-2,2 -bipyridine) (Cas-IIIia (4)) to human serum albumin (HSA) by circular dichroism (CD), Electron paramagnetic resonance (EPR) and fluorescence spectroscopy. The results indicate that HSA may bind up to three molecules of the tested Casiopeinas. This is confirmed by inductively coupled plasma atomic absorption spectroscopy measurements of samples of HSA-Casiopeinas after passing by adequate size-exclusion columns. The binding of Cas-II-Gly to HSA was also confirmed by MALDI-TOF mass spectrometric experiments. In the physiological range of concentrations the Casiopeinas form 1:1 adducts with HSA, with conditional binding constants of ca. 1 x 10(9) (1), 4 x 10(7) (2), 1 x 10(6) (3) and 2 x 10(5) (4), values determined from the CD spectra measured, and the fluorescence emission spectra indicates that the binding takes place close to the Trp214 residue. Overall, the data confirm that these Casiopeinas may bind to HSA and may be transported in blood serum by this protein; this might allow some selective tumor targeting, particularly in the case of Cas-Il-Gly. In this work we also discuss aspects associated to the reliability of the frequently used methodologies to determine binding constants based on the measurement of fluorescence emission spectra of solutions containing low concentrations of proteins such as HSA and BSA, by titration with solutions of metal complexes.
DOI http://dx.doi.org/10.1016/j.finorgbio.2017.07.025
ISBN
Publisher
Book Title
ISSN 0162-0134
EISSN 1873-3344
Conference Name
Bibtex ID ISI:000411919000032
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