Efficient and Selective Cleavage of RNA Oligonucleotides by Calix[4]arene-Based Synthetic Metallonucleases

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• 作者：Roberta Cacciapaglia ; Alessandro Casnati ; Luigi Mandolini ; Alessio Peracchi ; David N. Reinhoudt ; Riccardo Salvio ; Andrea Sartori ; Rocco Ungaro
• 刊名：Journal of the American Chemical Society
• 出版年：2007
• 出版时间：October 17, 2007
• 年：2007
• 卷：129
• 期：41
• 页码：12512 - 12520
• 全文大小：345K
• 年卷期：v.129,no.41(October 17, 2007)
• ISSN：1520-5126

文摘

Di- and trinuclear copper(II) complexes of [12]aneN₃ macrocycles anchored at the upper rim ofcone calix[4]arenes in 1,2-, 1,3-, and 1,2,3-positions were investigated as cleaving agents of 6-, 7-, and17-meric oligoribonucleotides. A kinetic investigation of the cleavage reactions was carried out using gelelectrophoresis to separate and analyze reactants and products having a radioactive phosphate label inthe terminal 5'-position. The degree of cooperation was assessed on the basis of a comparison with ratesof cleavage by mononuclear controls. A remarkable selectivity of cleavage of the CpA phosphodiesterbond was observed for all metal complexes, in sharp contrast with the UpU and UpG selectivity previouslyobserved in the cleavage of diribonucleoside monophosphates by the same metal complexes. The highestrate acceleration, brought about in the cleavage of the 5'-pCpA bond in hexanucleotide 9 by 50 M trinuclearcomplex 5-Cu₃ (water solution, pH 7.4, 50 C), amounts to 5 × 10⁵-fold, as based on the estimatedbackground 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-independentRNase A mimicks. The possible role of the dianionic phosphate at the 5'-terminal positions as a primaryanchoring site for the metal catalyst is discussed.