Kinetic study of azole-bridged dinuclear platinum(II) complexes reacting with a hairpin-stabilized double-stranded oligonucleotide.
The cytotoxic dinuclear platinum(II) complexes [[cis-Pt(NH(3))(2)](2)(mu-OH)(mu-pz)](NO(3))(2) (pz=pyrazolate) (1) and [[cis-Pt(NH(3))(2)](2)(mu-OH)(mu-1,2,3-ta-N1,N2)](NO(3))(2) (1,2,3-ta=1,2,3-triazolate) (2), were allowed to react with the hairpin-stabilized double-stranded oligonucleotide d(TATGGCATT(4)ATGCCATA), to determine the amounts of intrastrand and interstrand DNA adducts. The reaction kinetics was investigated by reversed-phase HPLC, and the resulting products were analyzed using mass spectroscopy combined with enzymatic digestion, and Maxam-Gilbert sequencing. The reaction of 1 results in the formation of the 1,2-intrastrand d(GG) adduct as the major final product. The two most abundant products of 2 were identified as isomeric 1,2-intrastrand d(GG) adducts differing probably in platinum coordination to the triazole ring. No GG-interstrand crosslinks were detected with either compound. d(GGC)-d(GCC) sequences of DNA do thus not appear to represent significant targets for forming interstrand crosslinks with either 1 or 2.
Komeda
Seiji
S
Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University P.O. Box 9502, 2300 RA, Leiden, The Netherlands.
Bombard
Sophie
S
Perrier
Sandrine
S
Reedijk
Jan
J
Kozelka
Jirí
J
D001393:Azoles; D001483:Base Sequence; D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid; D018736:DNA Adducts / Q000032:analysis / Q000737:chemistry; D007700:Kinetics; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*; D010984:Platinum / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D001393:Azoles; D018736:DNA Adducts; D009838:Oligodeoxyribonucleotides; D009942:Organometallic Compounds; D010984:Platinum