Time dependence of cisplatin-induced duplex dissociation of 15-mer RNAs and mature miR-146a

Abstract

The kinetics for the binding of cisplatin to duplex RNAs, two fully complementary model systems and mature miR-146a, exhibits a linear dependence on cisplatin concentration and results in duplex dissociation at 38 °C.

Synthesis and structures of a pincer-type rhodium(iii) complex: reactivity toward biomolecules

“…For such a reaction model, the second-order rate constant k 2,app can thus be directly obtained from the slope of a plot of k obsd vs. C (1) . 15,16 dsDNAðor dsRNAÞ þ ð1Þ ÀÀÀ* )ÀÀÀ…”

“…It turned out that the shorter 15GG duplex reacts faster than the longer 22GG duplex, which is consistent with previously published results. 15,16 Furthermore, the duplexes of the same length, but of different sequences, 22GG (DNA-2) and 22GTG (DNA-3) were studied. It was observed that a higher reactivity is achieved with a DNA duplex with a centrally located GG-sequence than with a 22GTG duplex in which the GG-sequence is separated by a T base.…”

Covalent and non-covalent binding of metal complexes to RNA

“…These findings suggest that mono-aquated cisplatin is able to discriminate in biological relevant salt concentration between different RNA targets [79]. The same approach was used to evaluate how platination kinetics are affected by the length of the duplex and the nature of bases surrounding the central GG platination site [70].…”

“…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).…”

“…Following this study, they established a quick methodology to investigate the platination kinetics of different RNA duplexes, that relies on monitoring platinum-induced duplex destabilization via UV-Vis spectroscopy in the presence of the mono-aquated form of cisplatin. Platination rate constants are obtained by following the changes of RNA absorbance in the presence of mono-aquated cisplatin as a function of time [79]. They first applied this method to study the platination kinetics of three RNA duplexes: two 15-nucleotide-long model RNAs, containing a GG and a GUG internal binding site, and a mature miRNA (RNA-1, RNA-2 and miR-146a in Fig.…”