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 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.
Bunkenborg
J
J
Department of Chemistry, University of Southern Denmark, Odense University, Odense M, DK-5230 Denmark.
Gadjev
N I
NI
Deligeorgiev
T
T
Jacobsen
J P
JP
D001483:Base Sequence; D052160:Benzothiazoles; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D019281:Dimerization; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D011804:Quinolines; D013844:Thiazoles / Q000737:chemistry / Q000378:metabolism*
D052160:Benzothiazoles; D011804:Quinolines; D013844:Thiazoles; C051000:thiazole orange; D004247:DNA