Proposed structure of the anthramycin-DNA adduct [25]

Laurence Hurley, Ruby Petrusek

Research output: Contribution to journalArticle

126 Citations (Scopus)

Abstract

Anthramycin, an antitumour antibiotic produced by Streptomyces refuineus1, belongs to the pyrrolo(1,4)benzodiazepine antibiotic group2. Antibiotics within this group are potent inhibitors of nucleic acid synthesis because of their ability to form a labile covalent adduct with DNA2-6. The reaction of anthramycin with DNA is unusual in that the rate of adduct formation is slow2,4,5, shows an absolute specificity for deoxyguanosine in a double-stranded template4, and is only stable as long as the secondary structure of DNA is retained6. Experiments using confluent non-dividing human cell lines have demonstrated that while repair-proficient cells are able to remove up to 84% of the adduct within 72 h, xeroderma pigmentosum cells in complementation group A were only able to remove 49% during the same incubation period10. We propose here a Corey, Pauling and Koltun (CPK) molecular model for the anthramycin-DNA adduct in which anthramycin is attached through the 2-amino group of guanine and lies hidden in the narrow groove. Experimental data supporting this model are provided. The model is based on information about the probable covalent binding sites on anthramycin and guanine together with the known crystal structure of anthramyin7.

Original languageEnglish (US)
Pages (from-to)529-531
Number of pages3
JournalNature
Volume282
Issue number5738
DOIs
StatePublished - 1979
Externally publishedYes

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Anthramycin
DNA Adducts
Guanine
Anti-Bacterial Agents
Nucleic Acid Synthesis Inhibitors
Xeroderma Pigmentosum
Deoxyguanosine
Molecular Models
Streptomyces
Binding Sites
Cell Line
DNA
anthramycin-DNA

ASJC Scopus subject areas

  • General

Cite this

Proposed structure of the anthramycin-DNA adduct [25]. / Hurley, Laurence; Petrusek, Ruby.

In: Nature, Vol. 282, No. 5738, 1979, p. 529-531.

Research output: Contribution to journalArticle

Hurley, Laurence ; Petrusek, Ruby. / Proposed structure of the anthramycin-DNA adduct [25]. In: Nature. 1979 ; Vol. 282, No. 5738. pp. 529-531.
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