DNA binding and cleavage of a novel antitumor antibiotic dynemicin A: detection of binding and cleavage sites by exonuclease III digestion and alkali-induced cutting reactions.
We found here that dynemicin A effectively breaks DNA strands under alkaline pH condition. Binding of dynemicin A to double-stranded DNA clearly interrupts the digestion reaction of exonuclease III. The DNA association sites of dynemicin A correspond considerably well to its cleavage sites. Dynemicin A seems to intercalate preferentially into the relaxed region of the DNA double helix. On the other hand, the alkali-product of dynemicin A was chromatographically identified with dynemicin N, suggesting a DNA cleavage mechanism similar to the reductant- and light-induced activation systems of dynemicin A. In order to detect drug binding to the relaxation structure in the DNA duplex, the present exonuclease III-digestion-stop-sequence method is useful.
Arakawa
T
T
Institute for Chemical Research, Kyoto University, Japan.
Kusakabe
T
T
Kuwahara
J
J
Otsuka
M
M
Sugiura
Y
Y
D000880:Anthraquinones / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D053281:Enediynes; D005090:Exodeoxyribonucleases / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data
D000880:Anthraquinones; D000903:Antibiotics, Antineoplastic; D053281:Enediynes; D004247:DNA; C061229:dynemicin A; D005090:Exodeoxyribonucleases; C020133:exodeoxyribonuclease III