Site-specific interaction of the antitumor antibiotic dynemicin with branched DNA molecules

M. Lu, Q. Guo, N. R. Kallenbach

Research output: Contribution to journalArticle

Abstract

A specific interaction of stable branched DNA molecules with the antitumor antibiotic dynemicin is reported. Dynemicin contains an anthraquinone and an enediyne unit, and belongs to the family of enediyne antitumor agents. DNA strand scission by dynemicin appears to involve interaction of the anthraquinone core with DNA and release of a phenyl diradical from the enediyne core that can abstract hydrogen atoms from the sugar phosphate backbone of DNA. The cleavage patterns of each labeled strand in two branched tetramers of four 16-mers are compared with those of the same strands in unbranched duplex controls. Differences between the profiles corresponding to scission of branched and duplex DNA molecules can be detected in most of the strands. The strongest differences define a specific site flanking the branch in each of two branched structures. At 18 °C, cleavage at strand positions demarcating the site of enhanced affinity in both junctions is observed to be 70-100% more efficient than at the corresponding sequence positions in the control duplex DNA molecules. The patterns of preferential cleavage at these sites are significantly altered in the presence of excess propidium diiodide, an intercalative drug.

Original languageEnglish (US)
Pages (from-to)271-283
Number of pages13
JournalJournal of Biomolecular Structure and Dynamics
Volume9
Issue number2
StatePublished - 1991

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Enediynes
Anti-Bacterial Agents
DNA
Anthraquinones
Sugar Phosphates
Propidium
Antineoplastic Agents
Hydrogen
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

Cite this

Site-specific interaction of the antitumor antibiotic dynemicin with branched DNA molecules. / Lu, M.; Guo, Q.; Kallenbach, N. R.

In: Journal of Biomolecular Structure and Dynamics, Vol. 9, No. 2, 1991, p. 271-283.

Research output: Contribution to journalArticle

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abstract = "A specific interaction of stable branched DNA molecules with the antitumor antibiotic dynemicin is reported. Dynemicin contains an anthraquinone and an enediyne unit, and belongs to the family of enediyne antitumor agents. DNA strand scission by dynemicin appears to involve interaction of the anthraquinone core with DNA and release of a phenyl diradical from the enediyne core that can abstract hydrogen atoms from the sugar phosphate backbone of DNA. The cleavage patterns of each labeled strand in two branched tetramers of four 16-mers are compared with those of the same strands in unbranched duplex controls. Differences between the profiles corresponding to scission of branched and duplex DNA molecules can be detected in most of the strands. The strongest differences define a specific site flanking the branch in each of two branched structures. At 18 °C, cleavage at strand positions demarcating the site of enhanced affinity in both junctions is observed to be 70-100{\%} more efficient than at the corresponding sequence positions in the control duplex DNA molecules. The patterns of preferential cleavage at these sites are significantly altered in the presence of excess propidium diiodide, an intercalative drug.",
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