RESUMO
An equilibrium containing the thiol derivative of Hoechst33258 (Ht-SH), glutathione (G-SH), and the corresponding homo and hetero disulfides was shifted by the addition of the duplex DNA. It was shown from the analysis of the components that the hetero disulfide Ht-SS-G increased by binding with the DNA (CA14) with an A(3)T(3) binding motif for the structure of Hoechst33258, and that the different equilibrium shift was observed in the presence of CT14 with no A(3)T(3) binding motif.
Assuntos
Bisbenzimidazol/análogos & derivados , DNA/química , Dissulfetos/química , Glutationa/química , Sequência de Bases , Ligantes , Oligonucleotídeos/química , OxirreduçãoRESUMO
The ligands (Bpy-H, 5) have been designed to connect the Hoechst33258 skeleton for DNA binding and 2,2'-bipyridine for Cu(2+) complexation. It has been revealed that the new Hoechst ligand long Bpy-H (5L) having a long linker exhibits Cu(2+)-mediated assembly on the DNA template having two A(3)T(3) sites in a selective manner depending on the length of the linker of the ligand as well as on the distance between the two A(3)T(3) sites of DNA. [reaction: see text]
Assuntos
Benzimidazóis/química , Cobre/química , DNA/química , Ligantes , Modelos Moleculares , Dados de Sequência Molecular , Estrutura Molecular , Conformação de Ácido Nucleico , Homologia de Sequência do Ácido NucleicoRESUMO
[structure: see text] The aim of this study is to develop bidentate minor-groove binders that bind the double binding motifs cooperatively. The new bidentate ligands (1) have been designed by connecting two Hoechst 33258 units with a polyether linker for cooperative binding with two remote A3T3 sites of DNA. The linker is introduced to the benzimidazole ring so that it is located at the convex side of the Hoechst unit. DNA binding affinity of the ligands was evaluated by measuring surface plasmon resonance (SPR), circular dichroism, and fluorescence spectra. Interestingly, the bidentate ligands (1) did not show affinity to DNA1 with a single A3T3 motif but showed selective affinity to DNA2 with two A3T3 motifs. The Long Bis-H (1L) having a long polyether linker showed specific binding to DNA2(6) with two A3T3 motifs separated by six nonbinding base pairs. The Long Bis-H (1L) has also shown specific binding to the three-way junction DNA4 with two A3T3 motifs. This study has demonstrated that DNA with double binding motifs can be selectively recognized by the newly designed bidentate ligands.
