title: Studies on the preferred uracil-adenine base pair at the cleavage site of 10-23 DNAzyme by functional group modifications on adenine.
abstract: 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-dA0 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-dA0 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 dA0 is favorable for the introduction of signal molecules for mechanistic studies and biological applications, without significant loss of the catalytic function and structural destruction.
authors.affiliation: College of Life Science, Guizhou University, Guiyang 550025, China.
authors.forename: Junfei
authors.initials: J
authors.lastname: Zhu
authors.affiliation: College of Life Science, Guizhou University, Guiyang 550025, China.
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Li
authors.affiliation: The State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China. Electronic address: yangzj@bjmu.edu.cn.
authors.forename: Zhenjun
authors.initials: Z
authors.lastname: Yang
authors.affiliation: College of Life Science, Guizhou University, Guiyang 550025, China; Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China. Electronic address: hejunlin@bmi.ac.cn.
authors.forename: Junlin
authors.initials: J
authors.lastname: He
mesh_terms: D000225:Adenine / Q000737:chemistry*; D020029:Base Pairing; D020134:Catalytic Domain; D060326:Chemistry Techniques, Synthetic; D002942:Circular Dichroism; D021881:DNA, Catalytic / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D004277:DNA, Single-Stranded / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D003839:Deoxyadenosines / Q000737:chemistry; D008345:Manganese / Q000737:chemistry; D014498:Uracil / Q000737:chemistry
chemical_list: D021881:DNA, Catalytic; D004277:DNA, Single-Stranded; D003839:Deoxyadenosines; C402582:RNA-cleaving DNA 10-23; D008345:Manganese; D014498:Uracil; D000225:Adenine
keywords: 10–23 DNAzyme; Chemical modification; Functional nucleic acid; Nucleoside analogs; Preferred cleavage site