Molybdenocene-oligonucleotide binding study at physiological pH using NMR spectroscopy and cyclic voltammetry.
Bioorg Med Chem
; 14(24): 8683-91, 2006 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-16945539
ABSTRACT
The self-complementary oligonucleotide CGCATATATGCG was used as a model to establish the binding interactions of antitumor molybdenocene dichloride and DNA. The free dodecamer was first characterized using (1)H, NOESY, and DQF-COSY NMR experiments, which enable to pinpoint the guanines and adenines as well as the cytosines and thymines signals in the aromatic region. Molybdenocene dichloride was characterized in saline and buffer solutions as function of pH by (1)H NMR spectroscopy. In 10mM NaCl/D(2)O solution at pH of 6.5 and above, Cp(2)Mo(OD)(D(2)O)(+) is in equilibrium with its dimeric species, [Cp(2)Mo(mu-OH)(2)MoCp(2)](2+). In 25mM Tris/4mM NaCl/D(2)O at physiological pH, a new stable species is formed, coordinated by the buffer, Tris(hydroxymethyl)aminomethane. The interactions of molybdenocene dichloride species with CGCATATATGCG were studied at different pH. At pH 6.5, in 4mM NaCl/D(2)O solution, (1)H NMR spectra of CGCATATATGCG exhibit downfield shifts in the signals associated mainly to adenines and guanines, upon addition of molybdenocene dichloride. At pH 7.4, in 25mM Tris/4mM NaCl/D(2)O, molybdenocene species causes broadening and small downfield shifts to the purines and pyrimidine signals, suggesting that molybdenocene dichloride can get engaged in binding interactions with the oligonucleotide in a weak manner. (31)P NMR spectra of these interactions at pH 7.4 showed no changes associated to Mo(IV)-OP coordination, indicating that molybdenocene-oligonucleotide binding interactions are centered, most likely, on the bases. Cyclic voltammetry titration showed a 4.9% of molybdenocene-oligonucleotide interaction. This implicates that possible binding interactions with DNA are weak.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligonucleotídeos
/
Compostos Organometálicos
/
DNA
/
Espectroscopia de Ressonância Magnética
/
Adutos de DNA
Idioma:
En
Revista:
Bioorg Med Chem
Ano de publicação:
2006
Tipo de documento:
Article