Design of new bidentate Ligands constructed of two Hoechst 33258 units for discrimination of the length of two A(3)T(3) binding motifs

• Published in: Journal of organic chemistry Vol. 71; no. 1; pp. 125 - 134
• Main Authors: Tanada, M, Tsujita, S, Sasaki, S
• Format: Journal Article
• Language: English
• Published: WASHINGTON Amer Chemical Soc 06.01.2006
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; SITE; RNA; SMALL-MOLECULE; CRYSTAL-STRUCTURE; DNA; TRANSCRIPTION; GENE-EXPRESSION; DRUG HOECHST-33258; G-QUADRUPLEX; D(CGCAAATTTGCG) DUPLEX
• ISSN: 0022-3263
• DOI: 10.1021/jo051836t

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 A(3)T(3) 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 A(3)T(3) motif but showed selective affinity to DNA2 with two A(3)T(3) 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 A(3)T(3) motifs. This study has demonstrated that DNA with double binding motifs can be selectively recognized by the newly designed bidentate ligands.