title: Highly efficient DNA compaction mediated by an in vivo antitumor-active tetrazolato-bridged dinuclear platinum(II) complex.
abstract: We investigated the effects of antitumor-active tetrazolato-bridged dinuclear platinum(II) complexes [{cis-Pt(NH(3))(2)}(2)(μ-OH)(μ-tetrazolato-N(1),N(2))](2+) (1) and [{cis-Pt(NH(3))(2)}(2)(μ-OH)(μ-tetrazolato-N(2),N(3))](2+) (2) on the higher-order structure of a large DNA molecule (T4 phage DNA, 166 kbp) in aqueous solution through single-molecule observation by fluorescence microscopy. Complexes 1 and 2 cause irreversible compaction of DNA through an intermediate state in which coil and compact parts coexist in a single DNA molecule. The potency of compaction is in the order 2 > 1 ≫ cisplatin. Transmission electron microscopic observation showed that both complexes collapsed DNA into an irregularly packed structure. Circular dichroism measurements revealed that the dinuclear platinum(II) complexes change the secondary structure of DNA from the B to C form. These characteristics of platinum(II) complexes are markedly different from those of the usual condensing agents such as spermidine(3+) and [Co(III)(NH(3))(6)](3+). The ability to cause DNA compaction by the platinum(II) complexes is discussed in relation to their potent antitumor activity.
authors: Department of Biotechnology, College of Life Sciences, Ritsumeikan University, Kusatsu 525-8577, Japan. yyoshi@fc.ritsumei.ac.jp
authors: Yuko
authors: Y
authors: Yoshikawa
authors: Seiji
authors: S
authors: Komeda
authors: Masako
authors: M
authors: Uemura
authors: Toshio
authors: T
authors: Kanbe
authors: Masahiko
authors: M
authors: Chikuma
authors: Kenichi
authors: K
authors: Yoshikawa
authors: Tadayuki
authors: T
authors: Imanaka
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D017122:Bacteriophage T4 / Q000187:drug effects; D002942:Circular Dichroism; D004279:DNA, Viral / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D009690:Nucleic Acid Conformation / Q000187:drug effects*; D009944:Organoplatinum Compounds / Q000737:chemistry* / Q000494:pharmacology*; D013777:Tetrazoles / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D004279:DNA, Viral; D009944:Organoplatinum Compounds; D013777:Tetrazoles; C045574:1H-tetrazole