Product analyses in DNA strand scission by antitumor antibiotic elsamicin A.


Elsamicin A is an antitumor antibiotic with fascinating chemical structure and a good candidate for pharmaceutical development. Molecular mechanism of DNA backbone cleavage mediated by Fe(II)-elsamicin A has been examined. Product analysis using DNA sequencing gels and HPLC reveals the production of damaged DNA fragments bearing 3'-/5'-phosphate and 3'-phosphoglycolate termini associated with formation of free base. In addition, hydrazine-trapping experiments indicate that C-4' hydroxylated abasic sites are formed concomitant with DNA degradation by Fe(II)-elsamicin A. The results lead to the conclusion that the hydroxyl radical formed in Fe(II)-elsamicin A plus dithiothreitol system oxidizes the deoxyribose moiety via hydrogen abstraction predominantly at the C-4' carbon of the deoxyribose backbone and ultimately produces strand breakage of DNA.

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@article{Uesugi1992ProductAI, title={Product analyses in DNA strand scission by antitumor antibiotic elsamicin A.}, author={Minatsu Uesugi and Yoshihiro Sugiura}, journal={Biochemical and biophysical research communications}, year={1992}, volume={186 1}, pages={580-7} }