Binding of cis- and trans-dichlorodiammineplatinum(II) to DNA: evidence for unwinding and shortening of the double helix
Abstract
The antitumor drug cis-dichlorodiammineplatinum(II) (cis-DDP) and the inactive trans isomer bind and produce cooperative changes in closed and nicked circular duplex DNA's. Covalent binding of both platinum complexes to the closed circular DNA alters the degree of supercoiling, presumably by disrupting and unwinding the double helix. Electron micrographs show the platinated DNA's to be shortened by up to 50 percent of their original length. At similar ratios of bound platinum per nucleotide, the electrophoretic mobilities of the DNA's in gels containing the dye ethidium bromide are the same for both isomers. The only detectable difference in the binding of the two platinum isomers is an increase in the electrophoretic mobility in nondye gels of closed circular DNA having small amounts of bound cis-DDP that is not apparent for the trans complex.
Additional Information
© 1979 American Association for the Advancement of Science. 21 September 1978; revised 18 December 1978. Supported by PHS grants CA-15826 from the National Cancer Institute (to S.J.L.) and GM-21176 from the National Institute of General Medical Sciences (to W.R.B.) and by NSF grant PCM76-01839 (to W.R.B.). J.K.B. thanks the National Science Foundation for a predoctoral fellowship. A generous gift of K_2PtCl_4 from Engelhard Industries used to prepare cis- and trans-DDP is gratefully acknowledged.Additional details
- Eprint ID
- 63989
- DOI
- 10.1126/science.370979
- Resolver ID
- CaltechAUTHORS:20160126-165802210
- CA-15826
- National Cancer Institute
- GM-21176
- National Institute of General Medical Sciences
- PCM76-01839
- NSF
- NSF Predoctoral Fellowship
- Created
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2016-01-27Created from EPrint's datestamp field
- Updated
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2021-11-10Created from EPrint's last_modified field