391903-22-3Relevant academic research and scientific papers
Tris-benzimidazole derivatives: Design, synthesis and DNA sequence recognition
Ji, Yu-Hua,Bur, Daniel,H?sler, Walter,Schmitt, Valérie Runtz,Dorn, Arnulf,Bailly, Christian,Waring, Michael J.,Hochstrasser, Remo,Leupin, Werner
, p. 2905 - 2919 (2007/10/03)
Two tris-benzimidazole derivatives have been designed and synthesized based on the known structures of the bis-benzimidazole stain Hoechst 33258 complexed to short oligonucleotide duplexes derived from single crystal X-ray studies and from NMR. In both derivatives the phenol group has been replaced by a methoxy-phenyl substituent. Whereas one tris-benzimidazole carries a N-methyl-piperazine at the 6-position, the other one has this group replaced by a 2-amino-pyrrolidine ring. This latter substituent results in stronger DNA binding. The optimized synthesis of the drugs is described. The two tris-benzimidazoles exhibit high AT-base pair (bp) selectivity evident in footprinting experiments which show that five to six base pairs are protected by the tris-benzimidazoles as compared to four to five protected by the bis-benzimidazoles. The tris-benzimidazoles bind well to sequences like 5′-TAAAC, 5′-TTTAC and 5′-TTTAT, but it is also evident that they can bind weakly to sequences such as 5′-TATGTT-3′ where the continuity of an AT stretch is interrupted by a single G·C base pair.
