Work

The DNA cleavage mechanism of iron-bleomycin. Kinetic resolution of strand scission from base propenal release.

Year: 1986

Type: article

Abstract: The action of iron-bleomycin and O2 in cleaving DNA has been resolved into two kinetic events following the initial attack on DNA by the kinetically competent drug species, "activated bleomycin." At 4 degrees C, DNA strand scission, monitored both viscometrically and fluorimetrically (t1/2 = 2.5-5 min), precedes the release from DNA of nucleic base propenals, which is half complete in about 40 min. Therefore, a moderately stable intermediate consisting of cleaved DNA bearing a base propenal precursor is formed. The release of tritium from deoxyribose carbon-2 occurs at the time of DNA scission, which is consistent with the base propenal precursor retaining the deoxyribose-3'-phosphate bond. Specific mechanistic proposals are discussed.

Source: Journal of Biological Chemistry

DOI: 10.1016/s0021-9258(18)66659-1

Authors: R M Burger, S J Projan, S B Horwitz, J Peisach

Institution: Yeshiva University

Language: English

Topic: Metal-Catalyzed Oxygenation Mechanisms

Subfield: Inorganic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: hybrid

Estimated APC paid: $3,430

Funders: National Cancer Institute, National Institute of General Medical Sciences