Triple-helix directed cleavage of double-stranded DNA by benzoquinoquinoxaline-1,10-phenanthroline conjugates.
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.
Zaid
Ahmed
A
Department of Molecular Biology & Functional Genomics, Stockholm University, 10691 Stockholm, Sweden.
Sun
Jian-Sheng
JS
Nguyen
Chi-Hung
CH
Bisagni
Emile
E
Garestier
Thérèse
T
Grierson
David S
DS
Zain
Rula
R
D003300:Copper / Q000737:chemistry; D004247:DNA / Q000737:chemistry*; D015195:Drug Design; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000737:chemistry*; D015394:Molecular Structure; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry*; D010618:Phenanthrolines / Q000138:chemical synthesis / Q000737:chemistry*; D010957:Plasmids / Q000737:chemistry; D011810:Quinoxalines / Q000138:chemical synthesis / Q000737:chemistry*
D007364:Intercalating Agents; D009841:Oligonucleotides; D010618:Phenanthrolines; D011810:Quinoxalines; C051802:triplex DNA; D003300:Copper; D004247:DNA; C025205:1,10-phenanthroline