Some characteristics of DNA strand scission by macromolecular antitumor antibiotic C-1027 containing a novel enediyne chromophore.
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Sugiura Y, Matsumoto T
Some characteristics of DNA strand scission by macromolecular antitumor antibiotic C-1027 containing a novel enediyne chromophore.
Biochemistry. 1993 Jun 1;32(21):5548-53.
- PubMed ID
- 8504075 [ View in PubMed]
- Abstract
A new macromolecular antitumor antibiotic, C-1027, shows potent cytotoxic effects and DNA cutting activity. The DNA cleaving properties of C-1027 are compared with those of other enediyne compounds such as neocarzinostatin, esperamicin A1, and calicheamicin gamma 1. Even in the absence of thiols or reductants, the antibiotic C-1027 has high DNA breakage ability. Of special interest is the fact that C-1027 causes strand breaks two base pairs apart at specific sites such as 5'-TAT/3'-ATA and 5'-AGA/3'-TCT (cleavage sites in italics) in the two strands. This novel double-stranded cleavage fashion is different from that of calicheamicin gamma 1, which is found to have a 3-bp separation between cleavage sites on the two strands. The asymmetric cleavage pattern to the 3'-side and a competitive experiment with distamycin A reveal minor-groove interaction of double-helical DNA with C-1027. This antibiotic appears to oxidize DNA through hydrogen abstraction predominantly at the C-4' carbon of deoxyribose. The activation mechanism of C-1027, which contains an enediyne chromophore of the esperamicin/calicheamicin type, has been proposed.