TAILIEUCHUNG - Báo cáo khoa học: DNA sequence specificity of triplex-binding ligands

We have examined the ability of naphthylquinoline, a 2,7-disubstituted anthraquinone and BePI, a benzo[e]pyri-doindole derivative, to stabilize parallel DNA triplexes of different base composition. 1 Fluorescence melting studies, with both inter- and intramolecular triplexes, show that all three ligands stabilize triplexes that contain blocks of TAT has no effect on triplexes formed with third strands composed of (TC)nor (CCT)n, but sta-bilizes triplexes that contain (TTC)n | Eur. J. Biochem. 270 4982-4992 2003 FEBS 2003 doi DNA sequence specificity of triplex-binding ligands Melanie D. Keppler Peter L. James1 Stephen Neidle2 Tom Brown3 and Keith R. Fox1 1 Division of Biochemistry Molecular Biology School of Biological Sciences University of Southampton UK 2CRC Biomolecular Structure Unit Cancer Research UK The School of Pharmacy University of London UK 3Department of Chemistry University of Southampton UK We have examined the ability of naphthylquinoline a 2 7-disubstituted anthraquinone and BePI a benzo e pyri-doindole derivative to stabilize parallel DNA triplexes of different base composition. Fluorescence melting studies with both inter- and intramolecular triplexes show that all three ligands stabilize triplexes that contain blocks of TAT triplets. Naphthylquinoline has no effect on triplexes formed with third strands composed of TC n or CCT n but stabilizes triplexes that contain TTC n. In contrast BePI slightly destabilizes the triplexes that are formed at TC n CCT n and TTC n. 2 7-Anthraquinone stabilizes TC n CCT n and TTC n although it has the greatest effect on the latter. DNase I footprinting studies confirm that triplexes formed with CCT n are stabilized by the 2 7-disubstituted amidoanthraquinone but not by naphthylquinoline. Both ligands stabilize the triplex formed with CCTT n and neither affects the complex with CT n. We suggest that BePI and naphthylquinoline can only bind between adjacent TAT triplets while the anthraquinone has a broader sequence of selectivity. These differences may be attributed to the presence naphthylquinoline and BePI or absence anthraquinone of a positive charge on the aromatic portion of the ligand which prevents intercalation adjacent to C GC triplets. The most stable structures are formed when the stacked rings bases or ligand alternate between charged and uncharged species. Triplexes containing alternating C GC and TAT triplets are not stabilized by ligands

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