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Titolo:
Kinetics of formation and stability of {Pt(dien)}(2+) complexes with octamer and 14-mer DNA oligonucleotides containing a GG sequence
Autore:
Murdoch, PD; Guo, ZJ; Parkinson, JA; Sadler, PJ;
Indirizzi:
Univ Edinburgh, Dept Chem, Edinburgh EH9 3JJ, Midlothian, Scotland Univ Edinburgh Edinburgh Midlothian Scotland EH9 3JJ Midlothian, Scotland
Titolo Testata:
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
fascicolo: 1, volume: 4, anno: 1999,
pagine: 32 - 38
SICI:
0949-8257(199902)4:1<32:KOFASO>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
SINGLE-STRANDED OLIGONUCLEOTIDES; FLIGHT MASS-SPECTROMETRY; INTRASTRAND CROSS-LINKS; PLATINUM BINDING-BASES; MONOFUNCTIONAL ADDUCTS; ANTITUMOR-ACTIVITY; NMR-SPECTROSCOPY; SOLID-STATE; CISPLATIN; PLATINATION;
Keywords:
platinum; oligonucleotide; monofunctional adducts; stability; kinetics;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
37
Recensione:
Indirizzi per estratti:
Indirizzo: Sadler, PJ Univhian,burgh, Dept Chem, Kings Bldg,W Mains Rd, Edinburgh EH93JJ, Midlot Univ Edinburgh Kings Bldg,W Mains Rd Edinburgh Midlothian Scotland EH9 3JJ
Citazione:
P.D. Murdoch et al., "Kinetics of formation and stability of {Pt(dien)}(2+) complexes with octamer and 14-mer DNA oligonucleotides containing a GG sequence", J BIOL I CH, 4(1), 1999, pp. 32-38

Abstract

Reaction of [Pl(dien)Cl](+) (1) with the 14-mer oligonucleotide 5'-d(ATACATGGTACATA) (I) gave rise to two major species which corresponded to the 5'-G and 3'-G platinated monofunctional adducts, and a minor amount of the bis-platinated adduct Formed during the later stages of the reaction. The reaction of (I) with the related octamer 5'-d(ATACATGC) (II) was also investigated. Kinetic data obtained by HPLC showed that the 5'-G and 3'-G bases of the 14-mer oligonucleotide were platinated at similar rates: the second-order rate constant is 53 x 10(-2) M-1 s(-1) at 298 K in 0.1 M NaClO4. However,the platination rate of 5'-G of the octamer (II) (k = 69 x 10(-2) M-1 s(-1)) was enhanced by a factor of three compared to the rate of platination at3'-G (k = 22 x 10(-2) M-1 s(-1)). All the adducts were separated by HPLC and characterized by NMR spectroscopy, enzymatic digestion and MALDI-TOF mass spectrometry. H-1 and N-15 NMR shifts suggest that there are distinct conformational differences between 14-mer duplexes platinated at 5'-G (I5'(ds)) and 3'-G (I3'(ds),). Molecular mechanics modelling indicates that rotation around the Pt-N7 bond is more restricted in the case of the 5'-G adduct than in that of the 3'-G adduct. The binding of {Pt(dien)}(2+) to 5 '-GN7 and 3'-GN7 in the monofunctional adducts of (I) was shown to be reversible upon the addition of high concentrations of chloride ions.

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Documento generato il 15/08/20 alle ore 19:54:38