Kinetic preference for interaction of cisplatin with the G–C-rich wobble basepair region in both tRNA<sup>Ala</sup>and Mh<sup>Ala</sup>

Papsai, Pal; Aldag, Jasmin; Persson, Therese; Elmroth, Sofi K. C.

doi:10.1039/b603833f

Cited by 26 publications

(29 citation statements)

References 25 publications

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“…Interestingly, the rate of initial product formation was found similar to that of cisplatin hydrolysis in the two cases, and a kinetic preference for adduct formation was observed at the wobble pair region in both constructs ( Fig. 3a and b), despite their differences in size and flexibility [77].…”

Section: Platinum Binding To Rnamentioning

confidence: 59%

“…Several examples of covalent binding of platinum complexes to RNA have been herein commented [44,45,47,70,[76][77][78][79][80][81][82][83][84][85][86][87]. Even if the existence of platinum-RNA adducts is undeniable, further biochemical and structural studies are needed to better understand the nature of platinum-RNA adducts as well as their impact on RNA structure and on RNA biological functions.…”

Section: Discussionmentioning

confidence: 95%

“…This preassociation precedes covalent interaction [90,91], and was shown to influence the binding kinetics also in model systems using short single-stranded DNAs [92]. This finding suggests that short RNAs may also represent good targets for cisplatin [77,78], and prompted further studies to better elucidate the basis of platinum-RNA interaction. Interestingly, in vitro studies performed using mono-aquated platinum complexes have shown that RNA platination kinetically competes or is even preferred over DNA platination [80,93].…”

Section: Platinum Binding To Rnamentioning

confidence: 90%

“…Moreover, GG sequences seem to be more readily platinated when they are in singlestranded regions than when they are involved in base-pairing like in the stem region. All of these findings suggest that small sequence variations, [77,78]. The GC-rich acceptor stem is indicated in grey; the GU wobble base-pair is indicated with a box; the UGC/GGC modification in the anticodon loop is indicated with contours.…”

Section: Platinum Binding To Rnamentioning

confidence: 96%

“…In the sections below the most recent advances in the elucidation of platinum-RNA interactions are summarized, mainly focusing on examples subsequent to the above-mentioned review [39]. In particular, the following aspects are covered: (i) RNA platination kinetics [45,70,[77][78][79] (Sections 3.1 and 3.2); (ii) some examples of platinum binding to structured RNAs [80], focusing on latest insights into platinum binding to ribosomal RNA [44,76,81] (Section 3.3); (iii) the effect of platination on RNA interference [82][83][84] (Section 3.4); (iv) the use of Pt-RNA adducts to study RNA structure and dynamics [85] (Section 3.5) and (v) recent methods to detect RNA-platinum adducts in cells [47,86,87] (Section 3.6).…”

Section: Platinum Binding To Rnamentioning

confidence: 99%

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Covalent and non-covalent binding of metal complexes to RNA

Alberti

Zampakou

Donghi

2016

Journal of Inorganic Biochemistry

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Targeting nucleic acids with metal complexes is an exciting and widely explored field of research. Following the discovery of the anticancer drug cisplatin, a number of metal complexes have been designed, synthesised, and tested for their DNA binding properties. On the contrary, the interaction of metal complexes with RNA has been much less investigated. RNA is an essential biomolecule, involved in a variety of crucial cellular functions, which offers a much wider structural diversity than DNA. As such, RNA represents an attractive target for the design and the development of structure-selective therapeutic and diagnostic agents. A few recent publications describe the ability of various metal complexes to interact with RNA, and the binding of cisplatin and derivatives to RNA is being currently investigated. This short review offers an overview of some recent advances on both covalent and non-covalent interactions of metal complexes with RNA and addresses the potential of targeting RNA non-duplex structures.

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Section: Platinum Binding To Rnamentioning

confidence: 59%

Section: Discussionmentioning

confidence: 95%

Section: Platinum Binding To Rnamentioning

confidence: 90%

Section: Platinum Binding To Rnamentioning

confidence: 96%

Section: Platinum Binding To Rnamentioning

confidence: 99%

See 3 more Smart Citations

Covalent and non-covalent binding of metal complexes to RNA

Alberti

Zampakou

Donghi

2016

Journal of Inorganic Biochemistry

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More pronounced salt dependence and higher reactivity for platination of the hairpin r(CGCGUUGUUCGCG) compared with d(CGCGTTGTTCGCG)

et al. 2006

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The DNA interference pathways exhibited by cisplatin and related anticancer active metal complexes have been extensively studied. Much less is known to what extent RNA interaction pathways may operate in parallel, and perhaps contribute to both antineoplastic activity and toxicity. The present study was designed with the aim of comparing the reactivity of two model systems comprising RNA and DNA hairpins, r(CGCGUUGUUCGCG) and d(CGCGTTGTTCGCG), towards a series of platinum(II) complexes. Three platinum complexes were used as metallation reagents; cis-[PtCl(NH3)2(OH2)]+ (1), cis-[PtCl(NH3)(c-C6H11NH2)(OH2)]+ (2), and trans-[PtCl(NH3)(quinoline)(OH2)]+ (3). The reaction kinetics were studied at pH 6.0, 25 degrees C, and 1.0 mM < or = I < or = 500 mM. For both types of nucleic acid targets, compound 3 was found to react about 1 order of magnitude more rapidly than compounds 1 and 2. Further, all platinum compounds exhibited a more pronounced salt dependence for the interaction with r(CGCGUUGUUCGCG). Chemical and enzymatic cleavage studies revealed similar interaction patterns with r(CGCGUUGUUCGCG) after long exposure times to 1 and 2. A substantial decrease of cleavage intensity was found at residues G4 and G7, indicative of bifunctional adduct formation. Circular dichroism studies showed that platinum adduct formation leads to a structural change of the ribonucleic acid. Thermal denaturation studies revealed platination to cause a decrease of the RNA melting temperatures by 5-10 degrees C. Our observations therefore suggest that RNA is a kinetically competitive target to DNA. Furthermore, platination causes destabilization of RNA structural elements, which may lead to deleterious intracellular effects on biologically relevant RNA targets.

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Cisplatin and siRNA interference with structure and function of Wnt-5a mRNA: design and in vitro evaluation of targeting AU-rich elements in the 3′ UTR

Hägerlöf¹,

Papsai²,

Hedman³

et al. 2007

J Biol Inorg Chem

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Wnt-5a is a secreted glycoprotein which has been shown to be involved in the regulation of cell adhesion and motility, processes which are of importance in metastasis formation by cancer cells. We here present an initial study aiming at evaluating whether small interfering RNA (siRNA) in combination with cisplatin can be used to modulate protein expression levels under in vitro conditions. For this purpose, an AU-rich region corresponding to the initial 260 bases of the Wnt-5a 3' untranslated region was chosen as the target. The effect of four different siRNAs was evaluated by analysis of protein suppression levels in rabbit reticulocyte lysate (RRL) and an immortalized noncancerous mammary epithelial (HB2) cell line by monitoring the activity of transiently expressed luciferase. The specificity and kinetics for hybridization of the siRNA with the messenger RNA target were followed by digestion techniques and analysis by polyacrylamide gel electrophoresis. Specific and temperature-dependent hybridization was observed, with a half-life of approximately 0.5 h at 4 degrees C. Significant downregulation of luciferase activity was obtained in the micromolar and nanomolar range, for RRL and HB2, respectively. In addition, the downregulation of protein production caused by addition of cisplatin could be further potentiated by addition of siRNA in a selective manner. The latter observation suggests that combined use of cisplatin and siRNA could be a method to decrease therapeutically used cisplatin concentrations. Thus, toxic side effects could be minimized while key proteins are targeted in a highly specific manner.

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Kinetic preference for interaction of cisplatin with the G–C-rich wobble basepair region in both tRNA^Alaand Mh^Ala

Abstract: The anticancer active complex cisplatin interacts preferentially with the common, G-C rich, wobble base pair region of both tRNA(Ala) and Mh(Ala) in a reaction that at pH 6.3 is rate limited by the acid hydrolysis of the metal complex.

Cited by 26 publications

References 25 publications

Covalent and non-covalent binding of metal complexes to RNA

Covalent and non-covalent binding of metal complexes to RNA

More pronounced salt dependence and higher reactivity for platination of the hairpin r(CGCGUUGUUCGCG) compared with d(CGCGTTGTTCGCG)

Cisplatin and siRNA interference with structure and function of Wnt-5a mRNA: design and in vitro evaluation of targeting AU-rich elements in the 3′ UTR

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Kinetic preference for interaction of cisplatin with the G–C-rich wobble basepair region in both tRNAAlaand MhAla

Abstract: The anticancer active complex cisplatin interacts preferentially with the common, G-C rich, wobble base pair region of both tRNA(Ala) and Mh(Ala) in a reaction that at pH 6.3 is rate limited by the acid hydrolysis of the metal complex.

Cited by 26 publications

References 25 publications

Covalent and non-covalent binding of metal complexes to RNA

Covalent and non-covalent binding of metal complexes to RNA

More pronounced salt dependence and higher reactivity for platination of the hairpin r(CGCGUUGUUCGCG) compared with d(CGCGTTGTTCGCG)

Cisplatin and siRNA interference with structure and function of Wnt-5a mRNA: design and in vitro evaluation of targeting AU-rich elements in the 3′ UTR

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Kinetic preference for interaction of cisplatin with the G–C-rich wobble basepair region in both tRNA^Alaand Mh^Ala