Concerted Intercalation and Minor Groove Recognition of DNA by a Homodimeric Thiazole Orange Dye

The thiazole orange dye TOTO binds to double-stranded DNA (dsDNA) by a sequence selective bis-intercalation. Each chromophore is sandwiched between two base pairs in a (5‘-CpT-3‘):(5‘-ApG-3‘) site, and the linker spans two base pairs in the minor groove. We have used one- and two-dimensional NMR spe...

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Bibliographic Details
Published in:Bioconjugate chemistry 2000-11, Vol.11 (6), p.861-867
Main Authors: Bunkenborg, Jakob, Gadjev, Nikolai I, Deligeorgiev, Todor, Jacobsen, Jens Peter
Format: Article
Language:English
Subjects:
Base Sequence
Benzothiazoles
Dimerization
DNA - chemistry
DNA - metabolism
Models, Molecular
Nuclear Magnetic Resonance, Biomolecular
Quinolines
Thiazoles - chemistry
Thiazoles - metabolism
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Summary:The thiazole orange dye TOTO binds to double-stranded DNA (dsDNA) by a sequence selective bis-intercalation. Each chromophore is sandwiched between two base pairs in a (5‘-CpT-3‘):(5‘-ApG-3‘) site, and the linker spans two base pairs in the minor groove. We have used one- and two-dimensional NMR spectroscopy to examine the dsDNA binding of an analogue of TOTO in which the linker has been modified to contain a bipyridyl group (viologen) that has minor groove binding properties. We have investigated the binding of this analogue, called TOTOBIPY, to three different dsDNA sequences containing a 5‘-CTAG-3‘, a 5‘-CTTAG-3‘, and a 5‘-CTATAG-3‘ sites, respectively, demonstrating that TOTOBIPY prefers to span three base pairs. The many intermolecular NOE connectivities between TOTOBIPY and the d(CGCTTAGCG):d(CGCTAAGCG) oligonucleotide in the complex shows that the bipyridyl-containing linker is positioned in the minor groove and spans three base pairs. Consequently, we have succeeded in designing and synthesizing a ligand that recognizes an extended recognition sequence of dsDNA as the result of a concerted intercalation and minor groove binding mode.
ISSN:1043-1802
1520-4812
DOI:10.1021/bc000042c