Determination of dna cleavage specificity by esperamicins

The esperamicins are members of a class of potent antitumor antibiotics that contain strained diacetylenic ring sytems 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.