Ligase-mediated synthesis of Cu(II)-responsive allosteric DNAzyme with bifacial 5-carboxyuracil nucleobases

连接酶介导的具有双面5-羧基尿嘧啶核碱基的Cu(II)响应性变构DNA酶的合成

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Abstract

A Cu(II)-responsive allosteric DNAzyme has been developed by introducing bifacial 5-carboxyuracil (caU) nucleobases, which form both hydrogen-bonded caU-A and metal-mediated caU-Cu(II)-caU base pairs. The base sequence was logically designed based on a known RNA-cleaving DNAzyme so that the caU-modified DNAzyme (caU-DNAzyme) can form a catalytically inactive structure containing three caU-A base pairs and an active form with three caU-Cu(II)-caU pairs. The caU-DNAzyme was synthesized by joining short caU-containing fragments with a standard DNA ligase. The activity of caU-DNAzyme was suppressed without Cu(II), but enhanced 21-fold with the addition of Cu(II). Furthermore, the DNAzyme activity was turned on and off during the reaction by the addition and removal of Cu(II) ions. Both ligase-mediated synthesis and Cu(II)-dependent allosteric regulation were achieved by the bifacial base pairing properties of caU. This study provides a new strategy for designing stimuli-responsive DNA molecular systems.

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