Nucleoapzymes: Hemin/G-Quadruplex DNAzyme–Aptamer Binding Site Conjugates with Superior Enzyme-like Catalytic Functions

详细信息    查看全文

• 作者：Eyal Golub ; H. Bauke Albada ; Wei-Ching Liao ; Yonatan Biniuri ; Itamar Willner
• 刊名：Journal of the American Chemical Society
• 出版年：2016
• 出版时间：January 13, 2016
• 年：2016
• 卷：138
• 期：1
• 页码：164-172
• 全文大小：532K
• ISSN：1520-5126

文摘

A novel concept to improve the catalytic functions of nucleic acids (DNAzymes) is introduced. The method involves the conjugation of a DNA recognition sequence (aptamer) to the catalytic DNAzyme, yielding a hybrid structure termed “nucleoapzyme”. Concentrating the substrate within the “nucleoapzyme” leads to enhanced catalytic activity, displaying saturation kinetics. Different conjugation modes of the aptamer/DNAzyme units and the availability of different aptamer sequences for a substrate provide diverse means to design improved catalysts. This is exemplified with (i) The H₂O₂-mediated oxidation of dopamine to aminochrome using a series of hemin/G-quadruplex-dopamine aptamer nucleoapzymes. All nucleoapzymes reveal enhanced catalytic activities as compared to the separated DNAzyme/aptamer units, and the most active nucleoapzyme reveals a 20-fold enhanced activity. Molecular dynamics simulations provide rational assessment of the activity of the various nucleoapzymes. The hemin/G-quadruplex–aptamer nucleoapzyme also stimulates the chiroselective oxidation of l- vs d-DOPA by H₂O₂. (ii) The H₂O₂-mediated oxidation of N-hydroxy-l-arginine to l-citrulline by a series of hemin/G-quadruplex–arginine aptamer conjugated nucleoapzymes.