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Issue 38, 2008
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Platination of full length tRNAAla and truncated versions of the acceptor stem and anticodon loop

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Abstract

Nuclear DNA is a well characterized target for many low molecular metal-based drugs, with cisplatin and related antineoplastic compounds as typical examples. Much less is known concerning to what extent targeting of RNA may influence the activity spectrum of these types of drugs. In a preliminary communication by us (Papsai et al., Dalton Trans., 2006, 3515) we were able to show that the folded, three-dimensionally well defined structure of tRNAAla readily interacts with cisplatin. In the present study we have further analyzed the binding preferences within the preferentially targeted stem region (sMhAla) by modulation of the sequence around the G–U wobble base-pair and the net charge of the 3′ and 5′ ends. Our data show that the adduct profile is strongly influenced by the presence of the 5′ end phosphate group. Further, the adduct formation reaction can be prevented by replacement of the G–U wobble base-pair with the fully complementary G–C pair. To further investigate the influence from local sequence on the platination process, a model of the anticodon region (acMhAla) was also investigated. In the absence of consecutive guanine-residues in the stem- and anticodon regions, preferential platination was found to take place at the terminal AG-site in the stem region. However, after introduction of a GG-pair in the anticodon loop, platination was observed also here. At 37 °C, pH 6.3 and CPt = 0.10 mM the rate of platination was determined to be ca. 1 × 10−4 s−1, with the most rapid reaction observed for interaction with the anticodon model carrying two adjacent guanines in the single-stranded loop. Together, these data show that platination of RNA is highly sequence- and structure-dependent.

Graphical abstract: Platination of full length tRNAAla and truncated versions of the acceptor stem and anticodon loop

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Publication details

The article was received on 19 Dec 2007, accepted on 19 Jun 2008 and first published on 21 Aug 2008


Article type: Paper
DOI: 10.1039/B719542G
Citation: Dalton Trans., 2008, 5225-5234
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    Platination of full length tRNAAla and truncated versions of the acceptor stem and anticodon loop

    P. Papsai, Å. S. Snygg, J. Aldag and S. K. C. Elmroth, Dalton Trans., 2008, 5225
    DOI: 10.1039/B719542G

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