K Ryan1, E T Kool. 1. Department of Chemistry, University of Rochester, NY 14627, USA.
Abstract
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.
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.
Authors: Damian Ackermann; Thorsten L Schmidt; Jeffrey S Hannam; Chandra S Purohit; Alexander Heckel; Michael Famulok Journal: Nat Nanotechnol Date: 2010-04-18 Impact factor: 39.213
Authors: Amanda Acevedo-Jake; Andrew T Ball; Marzia Galli; Mikiembo Kukwikila; Mathieu Denis; Daniel G Singleton; Ali Tavassoli; Stephen M Goldup Journal: J Am Chem Soc Date: 2020-03-20 Impact factor: 15.419