Binding of Al(iii) to synthetic RNA and metal-mediated strand aggregation

Abstract

Over the last few years, focused interest in aluminum has been heightened by recent studies regarding its health effects. Its possible relation with chronic diseases makes it convenient to address more in depth the reactivity of aluminum with biologically relevant molecules. The present work investigates the interaction of the aluminum ion with two synthetic RNAs, poly(rA) and poly(rU), through a detailed thermodynamic and kinetic study. The trivalent aluminum ion was kept in solution by complexation with the cacodylate anion, even at neutral pH, thus making the study with biological molecules feasible. The results obtained by spectrophotometry, circular dichroism, viscometry and thermal stability measurements indicate that aluminium strongly interacts with single and duplex RNA structures. The kinetic experiments point out that, even though cacodylate is required to keep the metal in solution, it actually inhibits the reaction of aluminum with RNA as it converts the metal into an unreactive dimer species. Notably, further interaction occurred in an excess of the aluminum/cacodylate complex, inducing aggregation of single-stranded RNAs. An analysis of the kinetic data has shown that the modes of aggregation of the two RNAs differ and such a difference can be ascribed to the diverse polynucleotide secondary structures. The observed stabilization of multiple-stranded systems by aluminum can serve as a model for future studies due to the interest aroused by this metal in the study of non-canonical nucleic acid structures.