Studies on the preferred uracil-adenine base pair at the cleavage site of 10-23 DNAzyme by functional group modifications on adenine

被引:7
作者
Zhu, Junfei [1 ]
Li, Zhiwen [1 ]
Yang, Zhenjun [2 ]
He, Junlin [1 ,3 ]
机构
[1] Guizhou Univ, Coll Life Sci, Guiyang 550025, Peoples R China
[2] Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
[3] Beijing Inst Pharmacol & Toxicol, Beijing 100850, Peoples R China
基金
中国国家自然科学基金;
关键词
10-23; DNAzyme; Preferred cleavage site; Chemical modification; Functional nucleic acid; Nucleoside analogs; RNA CLEAVAGE; CATALYTIC CORE; A9; POSITION; DNA ENZYME; METAL-IONS; SEQUENCE; DEOXYRIBOZYMES; ENHANCEMENT; IMIDAZOLYL; CATIONS;
D O I
10.1016/j.bmc.2015.06.041
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
10-23 DNAzyme is capable of catalytically cleaving RNA substrates with the preferred cleavage sites rAU and rGU, in which the common base pair U-dA(0) forms between the substrate and the DNAzyme in the cleavage reaction. Here its conservation was studied with base modifications on dA and extra functional groups introduced. The nitrogen atom at 7- or 8-position of adenine was demonstrated to be equally important for the cleavage reaction, although it is not related to the thermal stability of the base pair. Deletion of 6-amino group led to decreased stability of the base pair and a slight slower reaction rate. Extra functional groups through 6-amino group were not favorably accommodated in the cleavage site. From these modifications at the level of functional groups, it demonstrated that the base pair U-dA(0) not only contributes to the recognition and binding stability, but also it is involved in the active catalytic center by its functional groups and base stacking. This kind of chemical modifications with 7-substituted 8-aza-7-deaza-2'-deoxyadenosine at dA(0) is favorable for the introduction of signal molecules for mechanistic studies and biological applications, without significant loss of the catalytic function and structural destruction. (C) 2015 Elsevier Ltd. All rights reserved.
引用
收藏
页码:4256 / 4263
页数:8
相关论文
共 42 条
[31]   Effect of metal ions and sequence of deoxyribozymes on their RNA cleavage activity [J].
Sugimoto, N ;
Okumoto, Y ;
Ohmichi, T .
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 2, 1999, (07) :1381-1386
[32]   Sensitive and Convenient Detection of microRNAs Based on Cascade Amplification by Catalytic DNAzymes [J].
Tian, Tian ;
Xiao, Heng ;
Zhang, Zhengan ;
Long, Yuelin ;
Peng, Shuang ;
Wang, Shaoru ;
Zhou, Xiang ;
Liu, Songmei ;
Zhou, Xin .
CHEMISTRY-A EUROPEAN JOURNAL, 2013, 19 (01) :92-95
[33]   LNAzymes: Incorporation of LNA-type monomers into DNAzymes markedly increases RNA cleavage [J].
Vester, B ;
Lundberg, LB ;
Sorensen, MD ;
Babu, BR ;
Douthwaite, S ;
Wengel, J .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2002, 124 (46) :13682-13683
[34]   Improved RNA cleavage by LNAzyme derivatives of DNAzymes [J].
Vester, B ;
Lundberg, LB ;
Sorensen, MD ;
Babu, BR ;
Douthwaite, S ;
Wengel, J .
BIOCHEMICAL SOCIETY TRANSACTIONS, 2004, 32 :37-40
[35]   Probing the Function of Nucleotides in the Catalytic Cores of the 8-17 and 10-23 DNAzymes by Abasic Nucleotide and C3 Spacer Substitutions [J].
Wang, Bin ;
Cao, Liqiang ;
Chiuman, William ;
Li, Yingfu ;
Xi, Zhen .
BIOCHEMISTRY, 2010, 49 (35) :7553-7562
[36]   From Cascaded Catalytic Nucleic Acids to Enzyme-DNA Nanostructures: Controlling Reactivity, Sensing, Logic Operations, and Assembly of Complex Structures [J].
Wang, Fuan ;
Lu, Chun-Hua ;
Willner, Itamar .
CHEMICAL REVIEWS, 2014, 114 (05) :2881-2941
[37]   A Structure-Activity Relationship Study for 2′-Deoxyadenosine Analogs at A9 Position in the Catalytic Core of 10-23 DNAzyme for Rate Enhancement [J].
Wang, Qi ;
Zhang, Di ;
Liu, Yang ;
Cheng, Maosheng ;
He, Junlin ;
Liu, Keliang .
NUCLEIC ACID THERAPEUTICS, 2012, 22 (06) :423-427
[38]   Deletion analysis in the catalytic region of the 10-23 DNA enzyme [J].
Zaborowska, Z ;
Schubert, S ;
Kurreck, J ;
Erdmann, VA .
FEBS LETTERS, 2005, 579 (02) :554-558
[39]   Sequence requirements in the catalytic core of the "10-23" DNA enzyme [J].
Zaborowska, Z ;
Fürste, JP ;
Erdmann, VA ;
Kurreck, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (43) :40617-40622
[40]  
Zhang L, 2002, CANCER RES, V62, P5463