Efficient Access to Peptidyl-RNA Conjugates for Picomolar Inhibition of Non-ribosomal FemX<sub>Wv</sub>Aminoacyl Transferase
作者:Matthieu Fonvielle、Dénia Mellal、Delphine Patin、Maxime Lecerf、Didier Blanot、Ahmed Bouhss、Marco Santarem、Dominique Mengin-Lecreulx、Matthieu Sollogoub、Michel Arthur、Mélanie Ethève-Quelquejeu
DOI:10.1002/chem.201201999
日期:2013.1.21
various applications in studying the ribosome and enzymes participating in tRNA‐dependent pathways such as Fem transferases in peptidoglycan synthesis. Herein a convergent synthesis of peptidyl–RNAs based on Huisgen–Sharpless cycloaddition for the final ligation step is developed. Azides and alkynes are introduced into tRNA and UDP‐MurNAc‐pentapeptide, respectively. Synthesis of 2′‐azido RNA helix
肽基-RNA偶联物在研究核糖体和参与tRNA依赖性途径的酶(例如肽聚糖合成中的Fem转移酶)方面有多种应用。在此基础上,开发了基于Huisgen-Sharpless环加成法的最终连接步骤的肽基RNA聚合合成方法。叠氮化物和炔烃分别引入tRNA和UDP-MurNAc-五肽中。2'-叠氮基RNA螺旋的合成始于2'-叠氮基-2'-脱氧腺苷,其通过亚磷酰胺化学偶联至脱氧胞苷。产生的二核苷酸被脱保护,并通过T4 RNA连接酶连接至模拟Ala-tRNA Ala受体臂的22nt RNA螺旋。对于炔烃UDP-MurNAc-五肽,中观胱氨酸被酶促地掺入肽聚糖前体中并被还原,然后L- Cys与O-(间苯二甲磺酰基)羟胺转化为脱氢丙氨酸。丁3炔1硫醇与脱氢丙氨酸的反应可得到含炔的UDP-MurNAc-五肽。在三[[(1-羟丙基-1 H -1,2,3-三唑-4-基)甲基]胺]存在下,Cu I催化的叠氮化物炔烃环加