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Substitution‐Inert Trinuclear Platinum Complexes Efficiently Condense/Aggregate Nucleic Acids and Inhibit Enzymatic Activity
Author(s) -
Malina Jaroslav,
Farrell Nicholas P.,
Brabec Viktor
Publication year - 2014
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201408012
Subject(s) - chemistry , spermine , nucleic acid , dna , stereochemistry , hydrogen bond , platinum , enzyme , bioinorganic chemistry , nucleotide , topoisomerase , dna supercoil , molecule , biochemistry , organic chemistry , dna replication , catalysis , gene
Abstract The trinuclear platinum complexes (TriplatinNC‐A [{Pt(NH 3 ) 3 } 2 ‐μ‐{trans‐Pt(NH 3 ) 2 (NH 2 (CH 2 ) 6 NH 2 ) 2 }] 6+ , and TriplatinNC [{trans‐Pt(NH 3 ) 2 (NH 2 (CH 2 ) 6 NH 3 + )} 2 ‐μ‐{trans‐Pt(NH 3 ) 2 (NH 2 (CH 2 ) 6 NH 2 ) 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.