Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, 9190401, Israel.
Laboratory of Organic Chemistry, Wageningen University & Research, 6708 WE, Wageningen, The Netherlands.
Chembiochem. 2020 Jan 15;21(1-2):53-58. doi: 10.1002/cbic.201900182. Epub 2019 Jun 24.
Catalytic nucleic acids consisting of a bis-Zn -pyridyl-salen-type ([di-Zn 3,5 bis(pyridinylimino) benzoic acid]) complex conjugated to the ATP aptamer act as ATPase-mimicking catalysts (nucleoapzymes). Direct linking of the Zn complex to the 3'- or 5'-end of the aptamer (nucleoapzymes I and II) or its conjugation to the 3'- or 5'-end of the aptamer through bis-thymidine spacers (nucleoapzymes III and IV) provided a set of nucleoapzymes exhibiting variable catalytic activities. Whereas the separated bis-Zn -pyridyl-salen-type catalyst and the ATP aptamer do not show any noticeable catalytic activity, the 3'-catalyst-modified nucleoapzyme (nucleoapzyme IV) and, specifically, the nucleoapzyme consisting of the catalyst linked to the 3'-position through the spacer (nucleoapzyme III) reveal enhanced catalytic features in relation to the analogous nucleoapzyme substituted at the 5'-position (k =4.37 and 6.88 min , respectively). Evaluation of the binding properties of ATP to the different nucleoapzyme and complementary molecular dynamics simulations suggest that the distance separating the active site from the substrate linked to the aptamer binding site controls the catalytic activities of the different nucleoapzymes.
由双 Zn-吡啶-salen 型（[双 Zn3,5 双（吡啶亚氨基）苯甲酸]）配合物与 ATP 适体偶联而成的催化核酸充当 ATP 酶模拟催化剂（核酶）。将 Zn 配合物直接连接到适体的 3' 或 5' 端（核酶 I 和 II）或通过双胸腺嘧啶间隔物将其连接到适体的 3' 或 5' 端（核酶 III 和 IV），提供了一组具有可变催化活性的核酶。虽然分离的双 Zn-吡啶-salen 型催化剂和 ATP 适体没有显示出任何明显的催化活性，但 3' -催化剂修饰的核酶（核酶 IV），特别是通过间隔物连接到 3' 位的催化剂连接的核酶（核酶 III），与在 5' 位取代的类似核酶相比，显示出增强的催化特性（k =4.37 和 6.88 min，分别）。对不同核酶与 ATP 结合特性的评估和互补分子动力学模拟表明，将活性位点与与适体结合位点连接的底物分离的距离控制着不同核酶的催化活性。
