DNA strand scission by the novel antitumor antibiotic leinamycin
- Kyowa Hakko Kogyo Ltd, Tokyo (Japan)
Leinamycin is a recently discovered antitumor antibiotic with an unusual 1,3-dioxo-1,2-dithiolane structure. It preferentially inhibits the incorporation of ({sup 3}H)thymidine into the acid-insoluble fraction of Bacillus subtilis. In vitro, leinamycin causes single-strand cleavage of supercoiled double-helical pBR322 DNA in the presence of thiol cofactors. Scavengers of oxygen radical did not suppress the DNA-cleaving activity. Thiol-activated leinamycin binds calf thymus DNA at 4{degree}C and thermal treatment of the leinamycin-DNA adduct released a chemically modified leinamycin from the complex. The lack of cytotoxicity and DNA-cleaving activity for S-deoxyleinamycin indicates that the 1,3-dioxo-1,2-dithiolane moiety is essential for the activity of leinamycin. Thus, the primary cellular target of leinamycin appears to be DNA. It binds DNA and causes single-strand break at low concentrations, which may account for the potent antitumor activity.
- OSTI ID:
- 6253404
- Journal Information:
- Biochemistry; (USA), Journal Name: Biochemistry; (USA) Vol. 29:24; ISSN 0006-2960; ISSN BICHA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
62 RADIOLOGY AND NUCLEAR MEDICINE
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
ANTINEOPLASTIC DRUGS
AUTORADIOGRAPHY
AZINES
BACILLUS
BACILLUS SUBTILIS
BACTERIA
BIOLOGICAL EFFECTS
DNA
DRUGS
ELECTROPHORESIS
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
MICROORGANISMS
MOLECULAR STRUCTURE
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PYRIMIDINES
RIBOSIDES
STRAND BREAKS
THIOLS
THYMIDINE
TRITIUM COMPOUNDS