Determination of DNA cleavage specificity by esperamicins

M. Lu, Q. Guo, B. Krishnan, J. Golik, I. E. Rosenberg, T. W. Doyle, N. R. Kallenbach

Research output: Contribution to journalArticle

Abstract

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

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

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DNA Cleavage
DNA
Sulfhydryl Compounds
Hydrolysis
Anti-Bacterial Agents
esperamicin A1

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

Cite this

Lu, M., Guo, Q., Krishnan, B., Golik, J., Rosenberg, I. E., Doyle, T. W., & Kallenbach, N. R. (1991). Determination of DNA cleavage specificity by esperamicins. Journal of Biomolecular Structure and Dynamics, 9(2), 285-298.

Determination of DNA cleavage specificity by esperamicins. / Lu, M.; Guo, Q.; Krishnan, B.; Golik, J.; Rosenberg, I. E.; Doyle, T. W.; Kallenbach, N. R.

In: Journal of Biomolecular Structure and Dynamics, Vol. 9, No. 2, 1991, p. 285-298.

Research output: Contribution to journalArticle

Lu, M, Guo, Q, Krishnan, B, Golik, J, Rosenberg, IE, Doyle, TW & Kallenbach, NR 1991, 'Determination of DNA cleavage specificity by esperamicins', Journal of Biomolecular Structure and Dynamics, vol. 9, no. 2, pp. 285-298.
Lu M, Guo Q, Krishnan B, Golik J, Rosenberg IE, Doyle TW et al. Determination of DNA cleavage specificity by esperamicins. Journal of Biomolecular Structure and Dynamics. 1991;9(2):285-298.
Lu, M. ; Guo, Q. ; Krishnan, B. ; Golik, J. ; Rosenberg, I. E. ; Doyle, T. W. ; Kallenbach, N. R. / Determination of DNA cleavage specificity by esperamicins. In: Journal of Biomolecular Structure and Dynamics. 1991 ; Vol. 9, No. 2. pp. 285-298.
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