Abstract:
:Cisplatin analogues were synthesised that consisted of platinum(II) diamine complexes tethered via a polymethylene chain ( n = 3, 5, 8 and 10) to a phenanthridinium cation. Both chloro and iodo leaving groups were examined. DNA adduct formation was quantitatively analysed using a linear amplification system with the plasmid pGEM-3Zf(+). This system utilised Taq DNA polymerase to extend from an oligonucleotide primer to the damage site. This damage site inhibited the extension of the DNA polymerase. The products were electrophoresed on a DNA sequencing gel enabling adduct formation to be determined at base pair resolution. The damage intensity at each site was determined by densitometry. The platinum phenanthridinium complexes were shown to damage DNA at shorter incubation times than cisplatin. To produce similar levels of damage, an 18 h incubation was required for cisplatin compared to 30 min for the n = 3 platinum phenanthridinium complexes; this indicates that the intercalating chromophore causes a large increase in the rate of platination. A reaction mechanism involving direct displacement of the chloride by the N-7 of guanine may account for the rate increase. These results indicate that further development of these compounds could lead to more effective cancer chemotherapeutic agents.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Whittaker J,McFadyen WD,Wickham G,Wakelin LP,Murray Vdoi
10.1093/nar/26.17.3933subject
Has Abstractpub_date
1998-09-01 00:00:00pages
3933-9issue
17eissn
0305-1048issn
1362-4962pii
gkb648journal_volume
26pub_type
杂志文章abstract::The large terminase subunit is a central component of the genome packaging motor from tailed bacteriophages and herpes viruses. This two-domain enzyme has an N-terminal ATPase activity that fuels DNA translocation during packaging and a C-terminal nuclease activity required for initiation and termination of the packag...
journal_title:Nucleic acids research
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abstract::Unwanted side effects of drugs are a burden on patients and a severe impediment in the development of new drugs. At the same time, adverse drug reactions (ADRs) recorded during clinical trials are an important source of human phenotypic data. It is therefore essential to combine data on drugs, targets and side effects...
journal_title:Nucleic acids research
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/15.20.8511
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/24.17.3357
更新日期:1996-09-01 00:00:00
abstract::Three new proteins which selectively bind to UV-damaged DNA were identified and purified to near homogeneity from UV-irradiated Drosophila melanogaster embryos through several column chromatographies. These proteins, tentatively designated as D-DDB P1, P2 and P3, can be identified as different complex bands in a gel s...
journal_title:Nucleic acids research
pub_type: 杂志文章
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更新日期:1995-07-25 00:00:00
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/6.3.915
更新日期:1979-03-01 00:00:00
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/27.11.2241
更新日期:1999-06-01 00:00:00
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
pub_type: 杂志文章
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更新日期:1991-09-25 00:00:00
abstract::In mammalian cells, DNA damage induces robust changes in gene expression and these changes contribute to the proper execution of cellular responses to DNA damage, including DNA repair, cell cycle arrest and apoptosis. The transcription factor E2F-1 has been suggested to play a key role in the regulation of cell cycle-...
journal_title:Nucleic acids research
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更新日期:1999-01-15 00:00:00
abstract::The Cre-lox system is an important tool for genetic manipulation. To promote integrative reactions, two strategies using mutant lox sites have been developed. One is the left element/right element (LE/RE)-mutant strategy and the other is the cassette exchange strategy using heterospecific lox sites such as lox511 or l...
journal_title:Nucleic acids research
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更新日期:2002-10-01 00:00:00
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/16.5.2179
更新日期:1988-03-25 00:00:00
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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abstract::The nucleotide sequences 3' to the translational termination codons in a collection of human genes have been analysed for evidence of a preferred 3' context for natural UAG codons. The aim was to see whether human UAG contexts can be related to the recent demonstration of the effects of 3' context on nonsense suppress...
journal_title:Nucleic acids research
pub_type: 杂志文章
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journal_title:Nucleic acids research
pub_type: 杂志文章
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更新日期:2010-04-01 00:00:00
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journal_title:Nucleic acids research
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更新日期:2014-05-01 00:00:00
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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更新日期:2014-01-01 00:00:00
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/28.2.513
更新日期:2000-01-15 00:00:00
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journal_title:Nucleic acids research
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更新日期:2014-01-01 00:00:00