Efficient and selective cleavage of RNA oligonucleotides by calix[4] arene-based synthetic metallonucleases

Roberta Cacciapaglia, Alessandro Casnati, Luigi Mandolini, Alessio Peracchi, David Reinhoudt, Riccardo Salvio, R. Salvio, A. Sartori, Rocco Ungaro

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    Abstract

    Di- and trinuclear copper(II) complexes of [12]aneN3 macrocycles anchored at the upper rim of cone calix[4]arenes in 1,2-, 1,3-, and 1,2,3-positions were investigated as cleaving agents of 6-, 7-, and 17-meric oligoribonucleotides. A kinetic investigation of the cleavage reactions was carried out using gel electrophoresis to separate and analyze reactants and products having a radioactive phosphate label in the terminal 5‘-position. The degree of cooperation was assessed on the basis of a comparison with rates of cleavage by mononuclear controls. A remarkable selectivity of cleavage of the CpA phosphodiester bond was observed for all metal complexes, in sharp contrast with the UpU and UpG selectivity previously observed in the cleavage of diribonucleoside monophosphates by the same metal complexes. The highest rate acceleration, brought about in the cleavage of the 5‘-pCpA bond in hexanucleotide 9 by 50 μM trinuclear complex 5−Cu3 (water solution, pH 7.4, 50 °C), amounts to 5 × 105-fold, as based on the estimated background reactivity of the CpA dimer. Selectivity in the cleavage of oligoribonucleotides by copper(II) complexes closely resembles that experienced by ribonuclease A and by a number of metal-independent RNase A mimicks. The possible role of the dianionic phosphate at the 5‘-terminal positions as a primary anchoring site for the metal catalyst is discussed
    Original languageUndefined
    Pages (from-to)12512-12520
    Number of pages19
    JournalJournal of the American Chemical Society
    Volume129
    Issue number41
    DOIs
    Publication statusPublished - 2007

    Keywords

    • IR-74642
    • METIS-243311

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