Determination of DNA cleavage specificity by esperamicins.
The esperamicins are members of a class of potent antitumor antibiotics that contain stained diacetylenic ring systems capable of forming DNA-cleaving diradicals upon reaction with thiols. Here we show that the diacetylenic ring core itself determines the sequence specificity for scission of duplex DNA): esperamicin A1, and three products of hydrolysis of the glycon, esperamicins C, D, and E, are found to retain a common sequence preference. The sugar residues exert a strong influence on the cleavage efficiency, presumably by interacting nonspecifically with DNA. The presence of a branch in the DNA is found locally to inhibit scission by esperamicins, and this effect is shown to be due to the core also.
Lu
M
M
Department of Chemistry, New York University, New York 10003.
Guo
Q
Q
Krishnan
B
B
Golik
J
J
Rosenberg
I E
IE
Doyle
T W
TW
Kallenbach
N R
NR
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism*; D000903:Antibiotics, Antineoplastic / Q000378:metabolism*; D001483:Base Sequence; D002240:Carbohydrate Sequence; D004247:DNA / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D053281:Enediynes; D008969:Molecular Sequence Data
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D053281:Enediynes; D004247:DNA; C047543:esperamicin A1