Triple-Helix Directed Cleavage of Double-Stranded DNA by Benzoquinoquinoxaline-1,10-phenanthroline Conjugates

✍ Scribed by Ahmed Zaid; Jian-Sheng Sun; Chi-Hung Nguyen; Emile Bisagni; Thérèse Garestier; David S. Grierson; Rula Zain

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 338 KB
• Volume: 5
• Category: Article
• ISSN: 1439-4227
• DOI: 10.1002/cbic.200400074

✦ Synopsis

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 T**⋅**A×T base triplets.