DNA strand scission by the novel antitumor antibiotic leinamycin

Journal Article · Tue Jun 19 00:00:00 EDT 1990 · Biochemistry; (USA)

DOI:https://doi.org/10.1021/bi00476a005· OSTI ID:6253404

Hara, Mitsunobu; Saitoh, Yutaka; Nakano, Hirofumi ^[1]

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1. 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), Vol. 29:24; ISSN 0006-2960
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
ANTINEOPLASTIC DRUGS
BIOLOGICAL EFFECTS
DNA
AUTORADIOGRAPHY
ANTIBIOTICS
BACILLUS SUBTILIS
ELECTROPHORESIS
MOLECULAR STRUCTURE
STRAND BREAKS
THIOLS
THYMIDINE
TRITIUM COMPOUNDS
ANTI-INFECTIVE AGENTS
AZINES
BACILLUS
BACTERIA
DRUGS
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
MICROORGANISMS
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PYRIMIDINES
RIBOSIDES
550601* - Medicine- Unsealed Radionuclides in Diagnostics