The DNA cleavage mechanism of iron-bleomycin. Kinetic resolution of strand scission from base propenal release.
نویسندگان
چکیده
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.
منابع مشابه
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Computer analyses of DNA sequencing data obtained using various restriction fragments of pBR 322 DNA indicate that a trinucleotide sequence (-Pyr-G-C-) is the most preferred site for cleavage by the antitumor antibiotic bleomycin A2. Taliso mycin A, a structurally related bleomycin analog, cleaved at the sequences -G-T/Amost preferentially. However, the pres ence of a pyrimidine at the 5' side ...
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ورودعنوان ژورنال:
- The Journal of biological chemistry
دوره 261 34 شماره
صفحات -
تاریخ انتشار 1986