Most cited article - PubMed ID 18676645
Biophysical studies on the stability of DNA intrastrand cross-links of transplatin
Oligonucleotides modified by clinically ineffective trans-diamminedichloridoplatinum(II) (transplatin) have been shown to be effective modulators of gene expression. This is so because in some nucleotide sequences the 1,3-GNG intrastrand adducts formed by transplatin in double-helical DNA readily rearrange into interstrand cross-links so that they can cross-link the oligonucleotides to their targets. On the other hand, in a number of other sequences these intrastrand adducts are relatively stable, which represents the major difficulty in the clinical use of the antisense transplatin-modified oligonucleotides. Therefore, we examined in this study, the stability of 1,3-GNG intrastrand adducts in double-helical DNA formed by a new antitumor derivative of transplatin, trans-[Pt(CH3NH2)2Cl2], in the sequence contexts in which transplatin formed relatively stable intrastrand cross-links which did not readily rearranged into interstrand cross-links. We have found that 1,3-GNG intrastrand adducts in double-helical DNA formed by trans-[Pt(CH3NH2)2Cl2] even in such sequences readily rearrange into interstrand cross-links. This work also suggests that an enhanced frequency of intrastrand cross-links yielded by trans-[Pt(CH3NH2)2Cl2] is a consequence of the fact that these DNA lesions considerably distort double-helical DNA in far more sequence contexts than parent transplatin. Our results suggest that trans-[Pt(CH3NH2)2Cl2]-modified oligonucleotides represent promising candidates for new agents in antisense or antigene approach.
- MeSH
- DNA Adducts chemistry MeSH
- Cisplatin chemistry pharmacology MeSH
- DNA chemistry MeSH
- Humans MeSH
- Ligands MeSH
- Methylamines chemistry pharmacology MeSH
- Oligonucleotides chemistry pharmacology MeSH
- Antineoplastic Agents chemistry pharmacology MeSH
- Cross-Linking Reagents chemistry pharmacology MeSH
- Base Sequence MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- DNA Adducts MeSH
- Cisplatin MeSH
- DNA MeSH
- Ligands MeSH
- methylamine MeSH Browser
- Methylamines MeSH
- Oligonucleotides MeSH
- Antineoplastic Agents MeSH
- Cross-Linking Reagents MeSH
- transplatin MeSH Browser
