PMID:6291045

Citation	Van Dyke, MW, Hertzberg, RP and Dervan, PB (1982) Map of distamycin, netropsin, and actinomycin binding sites on heterogeneous DNA: DNA cleavage-inhibition patterns with methidiumpropyl-EDTA.Fe(II). Proc. Natl. Acad. Sci. U.S.A. 79:5470-4
Abstract	We report a direct technique for determining the binding sites of small molecules on naturally occurring heterogeneous DNA. Methidiumpropyl-EDTA.Fe(II) [MPE.Fe(II) cleaves double helical DNA with low sequence specificity. Using a combination of MPE.Fe(II) cleavage of drug-protected DNA fragments and Maxam-Gilbert gel methods of sequence analysis, we have determined the preferred binding sites on a Rsa I-EcoRI restriction fragment from pBR322 for the intercalator actinomycin D and the minor groove binders netropsin and distamycin A. Netropsin and distamycin A gave identical DNA cleavage-inhibition patterns and bound preferentially to A+T-rich regions with a minimal protected site of four base pairs. We were able to observe the effect of increasing concentration on site selection by netropsin and distamycin A. Actinomycin D afforded a completely different cleavage-inhibition pattern, with 4- to 16-base-pair-long protected regions centered around one or more G.C base pairs.
Links	PubMed PMC346925
Keywords	Chemical Phenomena; Chemistry; DNA, Bacterial; Dactinomycin; Daunorubicin; Distamycins; Escherichia coli; Guanidines; Netropsin; Plasmids; Pyrroles; Structure-Activity Relationship
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