Determination of dna cleavage specificity by esperamicins

Min Lu1 Qiu Guo, Bala Krishnan, Jerzy Golik, Ira E. Rosenberg, Terrence W. Doyle, Neville R. Kallenbach

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)285-298
Number of pages14
JournalJournal of Biomolecular Structure and Dynamics
Volume9
Issue number2
DOIs
StatePublished - Oct 1991

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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