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PMID: 8506383 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

DNA interstrand cross-links of trans-diamminedichloroplatinum(II) are preferentially formed between guanine and complementary cytosine residues.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 90 ·No. 11 ·1993-06-01 ·Pages 5345-9

Brabec V, Leng M

Abstract

Bases in the opposite strands of DNA cross-linked by clinically ineffective trans-diamminedichloroplatinum(II) (trans-[Pt(NH3)2Cl2]) have been identified by means of three experimental approaches. These include HPLC analysis of enzymatic digests of synthetic oligonucleotide duplexes containing the interstrand cross-link, footprinting experiments on the interstrand cross-linked oligonucleotide duplexes, and termination of the duplex transcription on trans-[Pt(NH3)2Cl2]-treated fragments of plasmid DNA. The results reveal that deoxyguanine and complementary deoxycytosine residues are preferential binding sites of trans-[Pt(NH3)2Cl2] in the interstrand adducts. The interstrand cross-linking reaction was studied by means of gel electrophoresis for the cis and trans isomers. The rate of formation of interstrand cross-links was lower for the trans isomer; however, trans-[Pt(NH3)2Cl2] formed about twice the amount of interstrand cross-links as compared with the cis isomer after 48 hr. The present results are suggested to be relevant to differences in clinical activity of the two platinum(II) isomers.

MeSH Terms
Base Sequence Cisplatin/chemistry,pharmacology Cross-Linking Reagents Cytosine DNA/chemistry Guanine Kinetics Molecular Sequence Data Oligodeoxyribonucleotides/chemical synthesis,chemistry Piperidines Restriction Mapping Structure-Activity Relationship Transcription, Genetic/drug effects
Chemicals
Cross-Linking Reagents Oligodeoxyribonucleotides Piperidines transplatin Guanine Cytosine DNA Cisplatin
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Brabec V
Centre de Biophysique Moléculaire, Centre National de la Recherche Scientifique, Orléans, France.
Leng M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.90.11.5345
Published
1993-06-01
Pages
5345-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC46713
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.90.11.5345 PMC Full Text View journal details
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