DNA binding studies of 7-bulky-substituted actinomycin analogues.
The DNA binding properties of several 7-substituted aralkylaminoactinomycin D analogues have been studied by spectrophotometry, DNA melting temperature studies, DNA-drug dissociation studies, and circular dichroism. Despite the presence of such bulky groups as 2-pyrrolylmethylamino or 3,4-dichlorobenzylamino at the 7 position, these analogues bind to DNA, inhibit RNA synthesis, and exhibit antitumor activity. A model is proposed for the interaction of the pyrrolyl analogue with phosphate groups of the DNA binding site, explaining the increased binding affinity for DNA of this actinomycin D analogue.
D000818:Animals; D002417:Cattle; D002942:Circular Dichroism; D004247:DNA / Q000378:metabolism*; D003609:Dactinomycin / Q000031:analogs & derivatives* / Q000378:metabolism; D006358:Hot Temperature; D009691:Nucleic Acid Denaturation
D003609:Dactinomycin; D004247:DNA