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Triple‐Helix Directed Cleavage of Double‐Stranded DNA by Benzoquinoquinoxaline‐1,10‐phenanthroline Conjugates
Author(s) -
Zaid Ahmed,
Sun JianSheng,
Nguyen ChiHung,
Bisagni Emile,
Garestier Thérèse,
Grierson David S.,
Zain Rula
Publication year - 2004
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200400074
Subject(s) - phenanthroline , triple helix , cleavage (geology) , chemistry , conjugate , dna , stereochemistry , helix (gastropod) , combinatorial chemistry , biochemistry , biology , crystallography , ecology , paleontology , fracture (geology) , snail , mathematical analysis , mathematics
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.