Study of the binding of cis- and trans-dichlorodiammineplatinum(II) to calf thymus DNA by extended x-ray absorption fine structure spectroscopy
Abstract
The complex cis-dichlorodiammineplatinum(II) (DDP) is an active antitumor drug while the trans-DDP isomer is ineffective, a result that may reflect differences in their ability to bind DNA.[1-5] While various chemical and physical techniques have been used to explore the interactions of these platinum compounds with DNA, there appears to be no direct structural information about the resulting platinum-DNA complex. Recent crystallographic study[5c] of the blue compound formed between cis-diammineplatinum and a-pyridone (1) suggested[5b] that thymine (2, R = CH3) and guanine (3) bases in DNA might bridge two cis-diammineplatinum units using the deprotonated amide nitrogen and the exocyclic oxygen as donor atoms. The resulting complex would have a short Pt-Pt distance, 2.5-3.2 A, depending upon the platinum oxidation state. To test this possibility and to provide information about the binding sites ofDDP, samples of cis- and trans-[Pt(NH3)iC!i] bound to calf thymus DNA, 4 and 5, respectively, were prepared and studied by extended x-ray absorption fine structure (EXAFS) spectroscopy.
Additional Information
© 1978 American Chemical Society. Received September 2, 1977. We thank Dr. B. M. Kincaid and Mr. A. L. Simons at Bell Laboratories for valuable assistance in data analysis and programming. We are also grateful to Dr. P.A. Lee (Bell Laboratories) for helpful discussions. The financial support of this work at Columbia was provided by a National Institutes of Health Grant No. CA-15826 from the National Cancer Institute to S.J.L. and by a National Science Foundation Predoctoral Fellowship to J.K.B. A generous loan of K_2PtC_(14) from Engelhard Industries is gratefully acknowledged. Synchrotron radiation was provided by the Stanford Synchrotron Radiation Laboratory supported by National Science Foundation Grant No. DMR 73-07692 in cooperation with the Stanford Linear Accelerator Center and the Energy Research and Development Administration.Additional details
- Eprint ID
- 78875
- Resolver ID
- CaltechAUTHORS:20170707-172652698
- CA-15826
- NIH
- NSF Predoctoral Fellowship
- Engelhard Industries
- DMR 73-07692
- NSF
- Stanford Linear Accelerator Center
- Energy Research and Development Administration (ERDA)
- Created
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2017-07-10Created from EPrint's datestamp field
- Updated
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2021-11-15Created from EPrint's last_modified field