Biophysical analysis of DNA modified by 1,2-diaminocyclohexane platinum(II) complexes
Jazyk angličtina Země Velká Británie, Anglie Médium print
Typ dokumentu časopisecké články
PubMed
1741252
PubMed Central
PMC310365
DOI
10.1093/nar/20.2.267
Knihovny.cz E-zdroje
- MeSH
- DNA chemie metabolismus MeSH
- guanosin chemie metabolismus MeSH
- kinetika MeSH
- konformace nukleové kyseliny MeSH
- molekulární sekvence - údaje MeSH
- oligodeoxyribonukleotidy chemie metabolismus MeSH
- organoplatinové sloučeniny chemie metabolismus MeSH
- protinádorové látky chemie metabolismus MeSH
- sekvence nukleotidů MeSH
- stereoizomerie MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- dichloro-1,2-diaminocyclohexane platinum complex MeSH Prohlížeč
- DNA MeSH
- guanosin MeSH
- oligodeoxyribonukleotidy MeSH
- organoplatinové sloučeniny MeSH
- protinádorové látky MeSH
Modification of DNA and double-stranded deoxyoligonucleotides with antitumour 1,2-diamino-cyclohexanedinitroplatinum(II) (Pt-dach) complexes was investigated with the aid of physico-chemical methods and chemical probes of nucleic acid conformation. The three Pt-dach complexes were used which differed in isomeric forms of the dach nonleaving ligand-Pt(1R,2R-dach), Pt(1S,2S-dach) and Pt(1R,2S-dach) complexes. The latter complex has lower antitumour activity than the other two Pt-dach complexes. Pt(1R,2S-dach) complex exhibits the slowest kinetics of its binding to DNA and of the conversion of monofunctional binding to bifunctional lesions. The anomalously slow electrophoretic mobility of multimers of the platinated and ligated oligomers suggests that bifunctional binding of Pt-dach complexes to a d(GG) site within double-stranded oligonucleotides induces bending of the oligomer. In addition, chemical probing of double-helical deoxyoligonucleotides modified by the Pt-dach complexes at the d(GG) sites reveals that Pt(1R,2S-dach) complex induces more extensive conformational changes in the oligomer than Pt(1R,2R-dach) and Pt(1S,2S-dach) complexes. It is proposed that different effects of the Pt-dach complexes on DNA observed in this work arise mainly from a steric crowding of the axially oriented cyclohexane ring in the DNA adduct of Pt(1R,2S-dach) complex.
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