TY - JOUR
T1 - Evaluation of the binding of four anti-tumor Casiopeínas® to human serum albumin
AU - Borovic, Sladjana
AU - Matos, Cristina P.
AU - Roy, Somnath
AU - Santos, Hugo M.
AU - Fernandes, Luz
AU - Capelo, José L.
AU - Pessoa, João Costa
AU - Correia, Isabel
AU - Ruiz-Azuara, Lena
N1 - sem pdf conforme despacho.
Fundacao para a Ciencia e Tecnologia (FCT), Portugal (projects UID/Multi/04349/2013, UID/QUI/00100/ 2013, RECl/QEQ-QIN/0189/2012, RECl/QEQ-MED/0330/2012), programme Investigador FCT: IF/00100/2013 (IC) and IF/00007/2015 (H.M.S.) and CONACYT 171991, Mexico.
Unidade de Ciencias Biomoleculares Aplicadas, (UID/Multi/04378/2013).
ERDF under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007728) and to the Associate Laboratory for Green Chemistry LAQV (UID/QUI/50006/ 2013) and co-financed by the ERDF under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007265)
PY - 2017/10/1
Y1 - 2017/10/1
N2 - The metal complexes designated by Casiopeínas® are mixed-ligand CuII-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-dimethyl-1,10-phenanthroline) (Cas-III-Ea (2)), Cu(glycinato)(4,4′-dimethyl-2,2′-bipyridine) (Cas-IV-Gly (3)) and Cu(acetylacetonato)(4,4′-dimethyl-2,2′-bipyridine) (Cas-III-ia (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 Casiopeínas. This is confirmed by inductively coupled plasma – atomic absorption spectroscopy measurements of samples of HSA-Casiopeínas 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 Casiopeínas form 1:1 adducts with HSA, with conditional binding constants of ca. 1 × 109 (1), 4 × 107 (2), 1 × 106 (3) and 2 × 105 (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 Casiopeínas 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-II-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 titrations with solutions of metal complexes.
AB - The metal complexes designated by Casiopeínas® are mixed-ligand CuII-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-dimethyl-1,10-phenanthroline) (Cas-III-Ea (2)), Cu(glycinato)(4,4′-dimethyl-2,2′-bipyridine) (Cas-IV-Gly (3)) and Cu(acetylacetonato)(4,4′-dimethyl-2,2′-bipyridine) (Cas-III-ia (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 Casiopeínas. This is confirmed by inductively coupled plasma – atomic absorption spectroscopy measurements of samples of HSA-Casiopeínas 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 Casiopeínas form 1:1 adducts with HSA, with conditional binding constants of ca. 1 × 109 (1), 4 × 107 (2), 1 × 106 (3) and 2 × 105 (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 Casiopeínas 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-II-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 titrations with solutions of metal complexes.
KW - Anti-tumor
KW - Binding constants
KW - Circular dichroism
KW - Copper complexes
KW - Fluorescence spectra
KW - Human serum albumin
UR - http://www.scopus.com/inward/record.url?scp=85028705251&partnerID=8YFLogxK
U2 - 10.1016/j.jinorgbio.2017.07.025
DO - 10.1016/j.jinorgbio.2017.07.025
M3 - Article
C2 - 28806645
AN - SCOPUS:85028705251
VL - 175
SP - 284
EP - 297
JO - Journal of Inorganic Biochemistry
JF - Journal of Inorganic Biochemistry
SN - 0162-0134
ER -