2-Deaminoactinomycin D, synthesis and interaction with deoxyribonucleic acid.
2-Deaminoactinomycin D has been synthesized and characterized. It binds to DNA by intercalation according to NMR, CD, thermal denaturation, and unwinding studies on the drug-DNA complex. Loss of the 2-amino group does not seriously affect binding parameters relative to actinomycin D; affinity for calf thymus DNA may even be increased, according to deltaTm measurements. The unwinding of circular DNA caused by this compound is at least as large as that effected by actinomycin D and ethidium bromide. Nevertheless, 2-deaminoactinomycin D is less effective than actinomycin D in inhibiting nucleic acid syntheses in L1210 cell culture and in in vivo antitumor activity against P388 leukemia.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis; D002478:Cells, Cultured; D002942:Circular Dichroism; D004247:DNA / Q000378:metabolism*; D004269:DNA, Bacterial; D004270:DNA, Circular; D004273:DNA, Neoplasm / Q000096:biosynthesis; D003609:Dactinomycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D003641:Deamination; D003864:Depression, Chemical; D004926:Escherichia coli; D066298:In Vitro Techniques; D007939:Leukemia L1210 / Q000378:metabolism; D007942:Leukemia, Experimental / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D009690:Nucleic Acid Conformation / Q000187:drug effects; D009691:Nucleic Acid Denaturation; D012334:RNA, Neoplasm / Q000096:biosynthesis
D000970:Antineoplastic Agents; D004269:DNA, Bacterial; D004270:DNA, Circular; D004273:DNA, Neoplasm; D012334:RNA, Neoplasm; D003609:Dactinomycin; D004247:DNA