Barton, Jacqueline K. and Lippard, Stephen J. (1979) Cooperative binding of a platinum metallointercalation reagent to poly(A)•poly(U). Biochemistry, 18 (12). pp. 2661-2668. ISSN 0006-2960. https://resolver.caltech.edu/CaltechAUTHORS:20160126-164902771
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Abstract
The cationic complex (2-hydroxyethanethiolato)(2,2',2"-terpyridine) platinum(II), [(terpy)Pt( HET)]^+, binds cooperatively to poly(A)•poly(U) by intercalation. The melting temperature of poly(A)•poly(U) in low-salt buffer is increased by 6 °C in the presence of [(terpy)Pt(HET)]^+, indicating stabilization of the duplex structure by the bound platinum reagent. Viscosity measurements provide evidence for comparable lengthening of the polynucleotide in the presence of [(terpy)Pt(HET)]^+ and the intercalating dye, ethidium bromide. Scatchard plots of the binding of [(terpy)Pt(HET)]^+ to poly(A)•poly(U) and poly(I)•poly(C), determined through ultracentrifugation pelleting methods, show large positive curvature, reflecting the strong cooperativity associated with the platinum complex-RNA interaction. The characteristics of the binding isotherms are interpreted in terms of a model where cooperative pair units of [(terpy)Pt(HET)]^+ intercalate into the double-stranded polymer. At saturation, two platinum molecules are bound for every three base pairs. This stoichiometry may be compared with the nearest-neighbor-exclusion binding observed previously in the interaction of [(terpy)Pt(HET)]^+ and the ethidium cation with DNA, in which one intercalator occupies every other interbase-pair site at saturation. The striking differences observed in the interaction of [(terpy)Pt(HET)]^+ with DNA and RNA suggest that drug recognition is sensitive to the constraints imposed by nucleic acid secondary structure.
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| Additional Information: | © 1979 American Chemical Society. Received January 10, 1979. This work was supported by National Institutes of Health Research Grant CA-15826 from the National Cancer Institute and by a National Science Foundation Predoctoral Fellowship to J.K.B. We thank J. Lehmann for excellent technical assistance. | |||||||||
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| Issue or Number: | 12 | |||||||||
| Record Number: | CaltechAUTHORS:20160126-164902771 | |||||||||
| Persistent URL: | https://resolver.caltech.edu/CaltechAUTHORS:20160126-164902771 | |||||||||
| Official Citation: | Cooperative binding of a platinum metallointercalation reagent to poly(A).cntdot.poly(U) Jacqueline K. Barton and Stephen J. Lippard Biochemistry 1979 18 (12), 2661-2668 DOI: 10.1021/bi00579a036 | |||||||||
| Usage Policy: | No commercial reproduction, distribution, display or performance rights in this work are provided. | |||||||||
| ID Code: | 63988 | |||||||||
| Collection: | CaltechAUTHORS | |||||||||
| Deposited By: | George Porter | |||||||||
| Deposited On: | 27 Jan 2016 19:16 | |||||||||
| Last Modified: | 03 Oct 2019 09:33 |
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