TY - JOUR
T1 - A comparative study of adduct formation between the anticancer ruthenium(III) compound HInd trans-[RuCl4(Ind)2] and serum proteins
AU - Piccioli, F
AU - Sabatini, S
AU - Messori, Luigi
AU - Orioli, P
AU - Hartinger, Christian
AU - Keppler, Bernhard
N1 - Zeitschrift: Journal of Inorganic Biochemistry
DOI: 10.1016/j.jinorgbio.2004.04.002
Coden: JIBID
Affiliations: Department of Chemistry, University of Florence, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Fi), Italy; Institute of Inorganic Chemistry, University of Vienna, Waehringer Strasse 42, A-1090 Vienna, Austria
Adressen: Messori, L.; Department of Chemistry; University of Florence; Via della Lastruccia 3 I-50019 Sesto Fiorentino (Fi), Italy; email: [email protected]
Source-File: ChemieErgScopus.csv
Import aus Scopus: 2-s2.0-2442449173
Importdatum: 09.01.2007 14:10:00
12.02.2008: Datenanforderung 2112 (Import Sachbearbeiter)
09.02.2010: Datenanforderung UNIVIS-DATEN-DAT.RA-2 (Import Sachbearbeiter)
PY - 2004
Y1 - 2004
N2 - Formation of adducts between the antitumor ruthenium(III) complex [HInd]trans-[RuCl4(Ind)2] (KP1019) and the plasma proteins serum albumin and serum transferrin was investigated by UV-vis spectroscopy, for metal-to-protein ratios ranging from 1:1 to 5:1. In both cases, formation of tight metal-protein conjugates was observed. Similar spectroscopic features were observed for both albumin and transferrin derivatives implying a similar binding mode of the ruthenium species to these proteins. Surface histidines are the probable anchoring sites for the bound ruthenium(III) ions in line with previous crystallographic results. In order to assess the stability of the KP1019-protein adducts the influence of pH, reducing agents and chelators was analysed by UV-vis spectroscopy. Notably, there was no effect of addition of EDTA on the UV-vis spectra of the conjugates. The pH-stability was high in the pH range 5-8. Experiments with sodium ascorbate showed that there was just some alteration of selected bands. The implications of the present results are discussed in relation to the pharmacological behavior of this novel class of antitumor compounds. Π2004 Elsevier Inc. All rights reserved.
AB - Formation of adducts between the antitumor ruthenium(III) complex [HInd]trans-[RuCl4(Ind)2] (KP1019) and the plasma proteins serum albumin and serum transferrin was investigated by UV-vis spectroscopy, for metal-to-protein ratios ranging from 1:1 to 5:1. In both cases, formation of tight metal-protein conjugates was observed. Similar spectroscopic features were observed for both albumin and transferrin derivatives implying a similar binding mode of the ruthenium species to these proteins. Surface histidines are the probable anchoring sites for the bound ruthenium(III) ions in line with previous crystallographic results. In order to assess the stability of the KP1019-protein adducts the influence of pH, reducing agents and chelators was analysed by UV-vis spectroscopy. Notably, there was no effect of addition of EDTA on the UV-vis spectra of the conjugates. The pH-stability was high in the pH range 5-8. Experiments with sodium ascorbate showed that there was just some alteration of selected bands. The implications of the present results are discussed in relation to the pharmacological behavior of this novel class of antitumor compounds. Π2004 Elsevier Inc. All rights reserved.
M3 - Article
SN - 0162-0134
VL - 98
SP - 1135
EP - 1142
JO - Journal of Inorganic Biochemistry
JF - Journal of Inorganic Biochemistry
IS - 6
ER -