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Triple-helix directed cleavage of double-stranded DNA by benzoquinoquinoxaline-1,10-phenanthroline conjugates.

Zaid, Ahmed; Sun, Jian-Sheng; Nguyen, Chi-Hung; Bisagni, Emile; Garestier, Thérèse; Grierson, David S; Zain, Rula.
Chembiochem; 5(11): 1550-7, 2004 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-15515089
Oligonucleotide-directed triple-helix formation provides a rational means to interfere with genomic DNA targets and to direct modifications at specific sites. We have developed a new class of compounds that, at low concentrations, efficiently targets and damages double-stranded DNA specifically at the site where a triple-helical structure is formed. In these new compounds, a triple-helix-specific intercalator-benzoquinoquinoxaline (BQQ)-was coupled to one of two isomeric 1,10-phenanthrolinecarboxaldehyde derivatives. 1,10-Phenanthroline derivatives are known to cleave DNA in the presence of copper ions. The obtained BQQ-1,10-phenanthroline (BQQ-OP) conjugates were compared with regard to their ability to cleave triple-helix DNA. Both conjugates displayed a sequence preference inside the triple-helical site, as judged from the more pronounced cleavage obtained at stretches of TAxT base triplets.
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