Bifunctional Rhodium Intercalator Conjugates as Mismatch-Directing DNA Alkylating Agents
Abstract
A conjugate of a DNA mismatch-specific rhodium intercalator, containing the bulky chrysenediimine ligand, and an aniline mustard has been prepared, and targeting of mismatches in DNA by this conjugate has been examined. The preferential alkylation of mismatched over fully matched DNA is found by a mobility shift assay at concentrations where untethered organic mustards show little reaction. The binding site of the Rh intercalator was determined by DNA photocleavage, and the position of covalent modification was established on the basis of the enhanced depurination associated with N-alkylation. The site-selective alkylation at mismatched DNA renders these conjugates useful tools for the covalent tagging of DNA base pair mismatches and new chemotherapeutic design.
Additional Information
© 2004 American Chemical Society. Received March 12, 2004. Publication Date (Web): June 24, 2004. We are grateful to the NIH (GM33309) for their financial support. We also thank the Deutsche Forschungsgemeinschaft for a postdoctoral fellowship (U.S.).Attached Files
Supplemental Material - ja048543msi20040511_043320.pdf
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Additional details
- Eprint ID
- 64334
- DOI
- 10.1021/ja048543m
- Resolver ID
- CaltechAUTHORS:20160209-121614706
- GM33309
- NIH
- Deutsche Forschungsgemeinschaft (DFG)
- Created
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2016-02-09Created from EPrint's datestamp field
- Updated
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2021-11-10Created from EPrint's last_modified field