Determination by Electrospray Mass Spectrometry of the Outersphere Association Constants of DNA/Platinum Complexes Using 20-mer Oligonucleotides and ([Pt(NH3)4]2+, 2Cl−) or ([Pt(py)4]2+, 2Cl−)

Autor: Nathalie Carte, Noelle Potier, Alain Van Dorsselaer, Franziska Reeder, Franck Legendre, Jean-Claude Chottard, Emmanuelle Leize
Přispěvatelé: Chimie de la matière complexe (CMC), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Rok vydání: 2000
Předmět:
Zdroj: Analytical Biochemistry
Analytical Biochemistry, Elsevier Masson, 2000, 284 (1), pp.77-86. ⟨10.1006/abio.2000.4661⟩
ISSN: 0003-2697
1096-0309
Popis: The cytotoxic effects of cisplatin, cis -diamminedichloroplatinum(II), are generally ascribed to the formation of DNA adducts. Several in vitro as well as in vivo studies showed that cisplatin binds preferentially to guanines belonging to (G) n sequences ( n ≥ 2). After mono- or diaquation of cisplatin, giving the cationic complexes cis -[PtCl(NH 3 ) 2 (H 2 O)] + and cis -[Pt(NH 3 ) 2 (H 2 O) 2 ] 2+ , DNA platination occurs in two steps: the cationic complex gives an outersphere association with DNA and the actual coordination then occurs by substitution of one aqua ligand by guanine-N7. For a better understanding of the (G) n selectivity of cisplatin giving the biologically active adducts, also necessary for the conception of new platinum drugs, the respective contribution of the outersphere association and actual guanine platination must be investigated. To check the role of outersphere association in the overall platination process, we used electrospray mass spectrometry (ESMS) to detect and quantify outersphere association between 20-mer oligonucleotides and platinum complexes. The 20-mer oligonucleotides were single- or double-stranded, with the same number of guanines either isolated or adjacent to each other. To deal only with outersphere association and check the influence of platinum ligands, the [Pt(NH 3 ) 4 ] 2+ and [Pt(py) 4 ] 2+ complexes were used. We characterized by ESMS all the different outersphere association species formed during titration of each oligonucleotide with the various platinum complexes and evaluated their affinity constants. The ESMS results demonstrate that the outersphere association depends on electrostatic interactions and on the ability of the platinum ligands to participate to hydrogen bonding, particularly within the duplex form.
Databáze: OpenAIRE
Externí odkaz: