Theantibiotic distamycin A isaDNAminorgroove binding drug(MGB)that recognizes astretch ofaleast fourATs.Thealkylating benzoyl mustard derivative tallimustine (FCE24517) haspowerfull anti-tumor activity. Using theelectrophoretic mobility shift assay (EMSA)we determined thatbothcompoundscan prevent binding ofTBP and,with10-fold higher concentration, TBP-TFIIA (DA)andTBP-TFIIA-TFIIB (DAB)toaTATAbox.Onceformed, theDAandDAB complexes aremoreresistant toMGBchallenge. Both drugscaninhibit basalinvitro transcription ofa minimal TATA-containing promoter andsimilar concentrations arenecessary forbinding andtranscriptional inhibition. Tallimustine showsstrong selectivity bydecreasing onlycorrectly initiated transcripts. Even athighdoses(20gM), however, theycannot disturb a competent pre-initiation complex orPol11progression. Thisfunctional invitro modelwill provide awayto investigate theactivity ofsequence-specific
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