DNA cleavage activity of liblomycin (NK313), a novel analog of bleomycin.

Publisher Website
Google Scholar
Abstract
Liblomycin (NK313), a novel analog of bleomycin and peplomycin (PEP), produced acid soluble DNA, base propenals and nucleo bases from isolated DNA. This was similar to the action of PEP. However, the DNA cleavage activity of NK313 was 1/2 .apprx. 1/10 of that of PEP in the absence of reducing agents. In the presence of reducing agents such as 2-mercaptoethanol and ascorbic acid, the activity of NK313 was stimulated more strongly than PEP. NK313 was also different from PEP in the formation and decomposition of active intermediates. This result suggested that differences in DNA cleavage activity between NK313 and PEP may be due to the different properties of their active intermediates. NK313 released preferentially pyrimidine bases from DNA, and the molar ratio of the released pyrimidine bases to the total of the released bases was little affected by the concentration of NK313 relative to DNA. In contrast, the ratio of the release purine bases by PEP increased with the concentration of PEP relative to DNA. NK313 induced double strand cleavage on pBR322 DNA as efficiently as did PEP. The major cleavage sites of NK313 on pBR322 DNA were similar to those of PEP. However, certain minor cleavage sites of NK313 were specific for NK313. Increase of PEP concentration led increase degradation of DNA fragments; this was not the case with NK313. These results indicate that the cleavage sites of NK313 were similar to, but more limited than those for PEP.