当前位置: X-MOL 学术J. Am. Chem. Soc. › 论文详情
Synthesis of a Nonhydrolyzable Nucleotide Phosphoroimidazolide Analogue That Catalyzes Nonenzymatic RNA Primer Extension
Journal of the American Chemical Society ( IF 13.858 ) Pub Date : 2018-01-02 , DOI: 10.1021/jacs.7b11623
Chun Pong Tam, Lijun Zhou, Albert C. Fahrenbach, Wen Zhang, Travis Walton, Jack W. Szostak

We report the synthesis of guanosine 5′-(4-methylimidazolyl)phosphonate (ICG), the third member of a series of nonhydrolyzable nucleoside 5′-phosphoro-2-methylimidazolide (2-MeImpN) analogues designed for mechanistic studies of nonenzymatic RNA primer extension. The addition of a 2-MeImpN monomer to a primer is catalyzed by the presence of a downstream activated monomer, yet the three nonhydrolyzable analogues do not show catalytic effects under standard mildly basic primer extension conditions. Surprisingly, ICG, which has a pKa similar to that of 2-MeImpG, is a modest catalyst of nonenzymatic primer extension at acidic pH. Here we show that ICG reacts with 2-MeImpC to form a stable 5′–5′-imidazole-bridged guanosine-cytosine dinucleotide, with both a labile nitrogen–phosphorus and a stable carbon–phosphorus linkage flanking the central imidazole bridge. Cognate RNA primer–template complexes react with this GC-dinucleotide by attack of the primer 3′-hydroxyl on the activated N–P side of the 5′-5′-imidazole bridge. These observations support the hypothesis that 5′–5′-imidazole-bridged dinucleotides can bind to cognate RNA primer–template duplexes and adopt appropriate conformations for subsequent phosphodiester bond formation, consistent with our recent mechanistic proposal that the formation of activated 5′–5′-imidazolium-bridged dinucleotides is responsible for 2-MeImpN-driven primer extension.
更新日期:2018-01-03

 

Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
分享到
评论: 0
期刊列表
南方科技大学“千人计划学者”讲座教授郑智平团队招聘启事
中山大学功能生物医用材料团队招聘博士后(待遇每年25万起)
华南理工大学生物科学与工程学院青年千人陈庭坚教授课题组招聘启事
东莞理工学院高薪招聘“有机合成/催化”博士后【48万年薪 + 若干科研启动费】
华南理工大学“青年千人”马志强课题组招聘启事
【问答】请问延长锂空气电池寿命的关键因素是什么?
2017年中科院JCR分区化学大类列表
试剂库存管理
化合物查询
down
wechat
bug