Sequence-specific recognition of double-stranded DNA by synthetic minor groove binder conjugates. toward the construction of artificial site-specific deoxyribonucleases.

Alexandre S Boutorine, Ludovic Halby, Philippe Simon, Loïc Perrouault, Carine Giovannangeli, Georgy V Gursky, Anna N Surovaya, Sergueï L Grokhovsky, Vladimir A Ryabinin, Alexandre N Sinyakov

Index: Nucleosides Nucleotides Nucleic Acids 26(10-12) , 1559-63, (2007)

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Abstract

Bis-conjugates of hairpin N-methylpyrrole/N-methylimidazole oligocarboxamide minor groove binders (MGB) possessing enhanced affinity and sequence-specificity for dsDNA were synthesized. Two hairpin MGBs were connected by their N-termini via an aminodiacetate linker. The binding of bis-MGB conjugates to the target DNA was studied by gel mobility retardation, footprinting, and circular dichroism; their affinity and binding mode in the DNA minor groove were determined. In order to functionalize the bis-MGB conjugates, DNA-cleaving agents such as phenanthroline or bipyridine were attached. Effective site-specific cleavage of target DNA in the presence of Cu(2+) ions was observed.