DNA sequence preferences of several AT-selective minor groove binding ligands.
We have examined the interaction of distamycin, netropsin, Hoechst 33258 and berenil, which are AT-selective minor groove-binding ligands, with synthetic DNA fragments containing different arrangements of AT base pairs by DNase I footprinting. For fragments which contain multiple blocks of (A/T)4 quantitative DNase I footprinting reveals that AATT and AAAA are much better binding sites than TTAA and TATA. Hoechst 33258 shows that greatest discrimination between these sites with a 50-fold difference in affinity between AATT and TATA. Alone amongst these ligands, Hoechst 33258 binds to AATT better than AAAA. These differences in binding to the various AT-tracts are interpreted in terms of variations in DNA minor groove width and suggest that TpA steps within an AT-tract decrease the affinity of these ligands. The behaviour of each site also depends on the flanking sequences; adjacent pyrimidine-purine steps cause a decrease in affinity. The precise ranking order for the various binding sites is not the same for each ligand.
Abu-Daya
A
A
Department of Physiology and Pharmacology, University of Southampton, UK.
Brown
P M
PM
Fox
K R
KR
D001482:Base Composition; D001483:Base Sequence; D001665:Binding Sites; D006690:Bisbenzimidazole / Q000737:chemistry*; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004133:Diminazene / Q000031:analogs & derivatives* / Q000737:chemistry; D004214:Distamycins / Q000737:chemistry*; D008024:Ligands; D008969:Molecular Sequence Data; D009429:Netropsin / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D013329:Structure-Activity Relationship
D004214:Distamycins; D008024:Ligands; D009429:Netropsin; C030000:stallimycin; D004247:DNA; C003915:diminazene aceturate; D006690:Bisbenzimidazole; D004133:Diminazene