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Cooperative binding of a platinum metallointercalation reagent to poly(A)•poly(U)

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. doi:10.1021/bi00579a036.

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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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Barton, Jacqueline K.0000-0001-9883-1600
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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National Cancer InstituteCA-15826
NSF Predoctoral FellowshipUNSPECIFIED
Issue or Number:12
Record Number:CaltechAUTHORS:20160126-164902771
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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
Deposited By: George Porter
Deposited On:27 Jan 2016 19:16
Last Modified:10 Nov 2021 23:24

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