Photofootprinting of drug‐binding sites‐on DNA using diazo‐ and azido‐9‐aminoacridine derivatives

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Abstract
It is demonstrated that DNA photofootprinting analysis of the intercalating depsipeptide echinomycin, and the minor groove-binders distamicyn, 4'',6-diamidino-2-phenylindole (DAPI) and Hoechst 33258 can be performed using 9-[6-(2-diazocyclopentadienylcarbonyloxy) hexylamino]acridine (DHA) [Nielsen et al. (1988) Nuclei acids Res. 16, 3877-3888] or 2-methoxy-6-azido-9-aminoacridine (MAA) [Jeppesen et al. (1988) Nucleic Acids Res. 16, 5755-5770]. Both the extent of the drug-binding sites and their relative strength can be determined with either reagent. DNA has the advantage of giving virtually sequence-uniform DNA photocleavage. On the other hand, structural changes in the DNA are detected by MAA. Using the 232-base-pair EcoRI-PvuII pUC19 restriction fragment, it is found that cleavage protection by distamycin, DAPI and Hoechst 33258 all require an (A .cntdot. T)4 sequence, whereas protection by echinomycin was confined to a G+C-rich 8-base-pair region.

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