Guanine-O6 Methylation Reduces the Reactivity of D(GpG) towards Platinum Complexes
(1991) In Journal of Inorganic Biochemistry 44(4). p.249-260- Abstract
- 06-methylated guanine dinucleotides were used to study the influence of hydrogen bonding on the specific binding of the antitumor drug cDDP, cis-PtCl2(NH3)2, to DNA. In this interaction, the guanine-06 site appears to be important in explaining the preference for a pGpG-N7(1),N7(2) chelate, which results from H-bridge formation with the ammine ligand of cDDP.Guanine-06 methylated dinucleotides and the nonmodified dinucleotides were reacted with [Pt(dien)Cl]+, cis-PtCl2(NH3)2, and cis-Pt(NH3)2(H2O)2]2+ and the reaction products were characterized by 1H NMR using pH titrations. Methylation at guanine-06 clearly reduces the preference for the guanine. In competition experiments monitored by NMR and experiments using UV spectrophotometry a... (More)
- 06-methylated guanine dinucleotides were used to study the influence of hydrogen bonding on the specific binding of the antitumor drug cDDP, cis-PtCl2(NH3)2, to DNA. In this interaction, the guanine-06 site appears to be important in explaining the preference for a pGpG-N7(1),N7(2) chelate, which results from H-bridge formation with the ammine ligand of cDDP.Guanine-06 methylated dinucleotides and the nonmodified dinucleotides were reacted with [Pt(dien)Cl]+, cis-PtCl2(NH3)2, and cis-Pt(NH3)2(H2O)2]2+ and the reaction products were characterized by 1H NMR using pH titrations. Methylation at guanine-06 clearly reduces the preference for the guanine. In competition experiments monitored by NMR and experiments using UV spectrophotometry a decreasing reactivity towards [Pt(dien)(H2O)]2+ and cis-[Pt(NH3)2(H2O)2]2+ was found, in the order of d(GpG) > d(GomepG) > d(GomepGome) > d(GomepGome). The difference in reactivity between 5′ guanine methylation and 3′ guanine methylation is ascribed to differences in the H-bond formation with the backbone phosphate. The resulting reduced stacking of the bases in both modified dinucleotides, compared to the bases in d(GpG), results in a preference for the 3′ guanine over 5′. (Less)
- Abstract (Swedish)
- 06-methylated guanine dinucleotides were used to study the influence of hydrogen bonding on the specific binding of the antitumor drug cDDP, cis-PtCl2(NH3)2, to DNA. In this interaction, the guanine-06 site appears to be important in explaining the preference for a pGpG-N7(1),N7(2) chelate, which results from H-bridge formation with the ammine ligand of cDDP.
Guanine-06 methylated dinucleotides and the nonmodified dinucleotides were reacted with [Pt(dien)Cl]+, cis-PtCl2(NH3)2, and cis-Pt(NH3)2(H2O)2]2+ and the reaction products were characterized by 1H NMR using pH titrations. Methylation at guanine-06 clearly reduces the preference for the guanine. In competition experiments monitored by NMR and experiments using UV spectrophotometry... (More) - 06-methylated guanine dinucleotides were used to study the influence of hydrogen bonding on the specific binding of the antitumor drug cDDP, cis-PtCl2(NH3)2, to DNA. In this interaction, the guanine-06 site appears to be important in explaining the preference for a pGpG-N7(1),N7(2) chelate, which results from H-bridge formation with the ammine ligand of cDDP.
Guanine-06 methylated dinucleotides and the nonmodified dinucleotides were reacted with [Pt(dien)Cl]+, cis-PtCl2(NH3)2, and cis-Pt(NH3)2(H2O)2]2+ and the reaction products were characterized by 1H NMR using pH titrations. Methylation at guanine-06 clearly reduces the preference for the guanine. In competition experiments monitored by NMR and experiments using UV spectrophotometry a decreasing reactivity towards [Pt(dien)(H2O)]2+ and cis-[Pt(NH3)2(H2O)2]2+ was found, in the order of d(GpG) > d(GomepG) > d(GomepGome) > d(GomepGome). The difference in reactivity between 5′ guanine methylation and 3′ guanine methylation is ascribed to differences in the H-bond formation with the backbone phosphate. The resulting reduced stacking of the bases in both modified dinucleotides, compared to the bases in d(GpG), results in a preference for the 3′ guanine over 5′. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/8d8cf13d-dc99-4673-abf5-0160b46e839c
- author
- Struik, A.F. ; Zuiderwijk, C.T.M. ; van Boom, J.H. ; Elding, Lars Ivar LU and Reedijk, Jan
- organization
- publishing date
- 1991-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- cisplatin, Antitumor drug, guanine dinucleotides, hydrogen bonding, NMR, UV-vis, Platinum(II)
- in
- Journal of Inorganic Biochemistry
- volume
- 44
- issue
- 4
- pages
- 249 - 260
- publisher
- Elsevier
- external identifiers
-
- scopus:0026334401
- ISSN
- 1873-3344
- DOI
- 10.1016/0162-0134(91)84030-D
- language
- English
- LU publication?
- yes
- id
- 8d8cf13d-dc99-4673-abf5-0160b46e839c
- date added to LUP
- 2017-01-08 21:27:46
- date last changed
- 2025-04-04 14:34:03
@article{8d8cf13d-dc99-4673-abf5-0160b46e839c,
abstract = {{06-methylated guanine dinucleotides were used to study the influence of hydrogen bonding on the specific binding of the antitumor drug cDDP, cis-PtCl2(NH3)2, to DNA. In this interaction, the guanine-06 site appears to be important in explaining the preference for a pGpG-N7(1),N7(2) chelate, which results from H-bridge formation with the ammine ligand of cDDP.Guanine-06 methylated dinucleotides and the nonmodified dinucleotides were reacted with [Pt(dien)Cl]+, cis-PtCl2(NH3)2, and cis-Pt(NH3)2(H2O)2]2+ and the reaction products were characterized by 1H NMR using pH titrations. Methylation at guanine-06 clearly reduces the preference for the guanine. In competition experiments monitored by NMR and experiments using UV spectrophotometry a decreasing reactivity towards [Pt(dien)(H2O)]2+ and cis-[Pt(NH3)2(H2O)2]2+ was found, in the order of d(GpG) > d(GomepG) > d(GomepGome) > d(GomepGome). The difference in reactivity between 5′ guanine methylation and 3′ guanine methylation is ascribed to differences in the H-bond formation with the backbone phosphate. The resulting reduced stacking of the bases in both modified dinucleotides, compared to the bases in d(GpG), results in a preference for the 3′ guanine over 5′.}},
author = {{Struik, A.F. and Zuiderwijk, C.T.M. and van Boom, J.H. and Elding, Lars Ivar and Reedijk, Jan}},
issn = {{1873-3344}},
keywords = {{cisplatin; Antitumor drug; guanine dinucleotides; hydrogen bonding; NMR; UV-vis; Platinum(II)}},
language = {{eng}},
number = {{4}},
pages = {{249--260}},
publisher = {{Elsevier}},
series = {{Journal of Inorganic Biochemistry}},
title = {{Guanine-O6 Methylation Reduces the Reactivity of D(GpG) towards Platinum Complexes}},
url = {{http://dx.doi.org/10.1016/0162-0134(91)84030-D}},
doi = {{10.1016/0162-0134(91)84030-D}},
volume = {{44}},
year = {{1991}},
}