Chemistry & biology · 1998
Triplex-directed self-assembly of an artificial sliding clamp on duplex DNA.
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Ryan K, Kool E T
Аннотация
BACKGROUND: Circular triplex-forming oligonucleotides (CTFOs) have previously been shown to bind tightly to short single-stranded homopurine DNAs in a sequence-specific manner. In view of the importance of double-stranded DNA as a target in the development of gene-specific therapeutic and diagnostic agents, we have investigated the binding of CTFOs to double-helical DNA.
RESULTS: DNA-binding experiments show that a CTFO can recognize its homopurine target when the target is embedded in a long duplex. Unlike their linear counterparts, CTFOs bind the double helix in two topologically distinct forms. The more stable of the two complexes is found to be a pseudorotaxane, having the same topology as the sliding clamp protein subunits associated with some DNA and RNA polymerases.
CONCLUSIONS: Circular triplex-forming oligonucleotides have been shown to bind the DNA double helix in a topological manner which is unprecedented among synthetic ligands. This novel binding motif allows a synthetic CTFO to be irreversibly locked onto a circular double-stranded DNA target without covalently modifying the target.
RESULTS: DNA-binding experiments show that a CTFO can recognize its homopurine target when the target is embedded in a long duplex. Unlike their linear counterparts, CTFOs bind the double helix in two topologically distinct forms. The more stable of the two complexes is found to be a pseudorotaxane, having the same topology as the sliding clamp protein subunits associated with some DNA and RNA polymerases.
CONCLUSIONS: Circular triplex-forming oligonucleotides have been shown to bind the DNA double helix in a topological manner which is unprecedented among synthetic ligands. This novel binding motif allows a synthetic CTFO to be irreversibly locked onto a circular double-stranded DNA target without covalently modifying the target.