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 ca...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1977-08, Vol.20 (8), p.1055-1059
Main Authors: Mosher, Carol W, Kuhlmann, Karl F, Kleid, Dennis G, Henry, David W
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - chemical synthesis
Cells, Cultured
Circular Dichroism
Dactinomycin - analogs & derivatives
Dactinomycin - chemical synthesis
Dactinomycin - metabolism
Deamination
Depression, Chemical
DNA - metabolism
DNA, Bacterial
DNA, Circular
DNA, Neoplasm - biosynthesis
Escherichia coli
In Vitro Techniques
Leukemia L1210 - metabolism
Leukemia, Experimental - drug therapy
Magnetic Resonance Spectroscopy
Mice
Nucleic Acid Conformation - drug effects
Nucleic Acid Denaturation
RNA, Neoplasm - biosynthesis
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Summary: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.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00218a013