title: Substitution-inert trinuclear platinum complexes efficiently condense/aggregate nucleic acids and inhibit enzymatic activity.
abstract: The trinuclear platinum complexes (TriplatinNC-A [{Pt(NH3 )3 }2 -μ-{trans-Pt(NH3 )2 (NH2 (CH2 )6 NH2 )2 }](6+) , and TriplatinNC [{trans-Pt(NH3 )2 (NH2 (CH2 )6 NH3 (+) )}2 -μ-{trans-Pt(NH3 )2 (NH2 (CH2 )6 NH2 )2 }](8+) ) are biologically active agents that bind to DNA through noncovalent (hydrogen bonding, electrostatic) interactions. Herein, we show that TriplatinNC condenses DNA with a much higher potency than conventional DNA condensing agents. Both complexes induce aggregation of small transfer RNA molecules, and TriplatinNC in particular completely inhibits DNA transcription at lower concentrations than naturally occurring spermine. Topoisomerase I-mediated relaxation of supercoiled DNA was inhibited by TriplatinNC-A and TriplatinNC at concentrations which were 60 times and 250 times lower than that of spermine. The mechanisms for the biological activity of TriplatinNC-A and TriplatinNC may be associated with their ability to condense/aggregate nucleic acids with consequent inhibitory effects on crucial enzymatic activities.
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i. Kralovopolska 135, CZ-61265 Brno (Czech Republic) http://www.ibp.cz/en/departments/molecular-biophysics-and-pharmacology/info-about-the-department.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Malina
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Farrell
authors.forename: Viktor
authors.initials: V
authors.lastname: Brabec
mesh_terms: D004247:DNA / Q000737:chemistry* / Q000187:drug effects*; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000494:pharmacology*; D010957:Plasmids; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D009944:Organoplatinum Compounds; D059004:Topoisomerase I Inhibitors; D004247:DNA; D004264:DNA Topoisomerases, Type I
keywords: DNA condensation; nucleic acids; platinum; tRNA; topoisomerase I