title: Triple-helix directed cleavage of double-stranded DNA by benzoquinoquinoxaline-1,10-phenanthroline conjugates.
abstract: 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.
authors.affiliation: Department of Molecular Biology & Functional Genomics, Stockholm University, 10691 Stockholm, Sweden.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Zaid
authors.forename: Jian-Sheng
authors.initials: JS
authors.lastname: Sun
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Nguyen
authors.forename: Emile
authors.initials: E
authors.lastname: Bisagni
authors.forename: Thérèse
authors.initials: T
authors.lastname: Garestier
authors.forename: David S
authors.initials: DS
authors.lastname: Grierson
authors.forename: Rula
authors.initials: R
authors.lastname: Zain
mesh_terms: 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*
chemical_list: D007364:Intercalating Agents; D009841:Oligonucleotides; D010618:Phenanthrolines; D011810:Quinoxalines; C051802:triplex DNA; D003300:Copper; D004247:DNA; C025205:1,10-phenanthroline