The DNA cleavage mechanism of iron-bleomycin. Kinetic resolution of strand scission from base propenal release.
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.
D001761:Bleomycin / Q000494:pharmacology* / Q000031:analogs & derivatives; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA / Q000378:metabolism*; D007700:Kinetics; D014316:Tritium
C023503:iron bleomycin; D014316:Tritium; D001761:Bleomycin; D004247:DNA