4'-三氟甲基尿苷修饰的寡核苷酸合成及修饰位点构象研究

Synthesis and Structure of 4'-CF_(3)-Uridine Modified Oligoribonucleotides

合成了4'-CF3修饰的尿苷亚磷酰胺单体,并通过固相合成将其引入了寡聚核苷酸链.分子动态模拟和NMR的结构研究,以及寡聚核苷酸的基本生化性质测定都表明4'-CF3修饰将该核苷酸的核糖锁定在不常见的South构象.

The synthesis and structure of 4'-CF3-uridine modified ribonucleotides are reported.Active 4'-CF3-uridine(4'-TfMU)phosphoramidite was prepared and successfully incorporated into oligonucleotides based on solid-supported synthesis.Molecular dynamics simulations and NMR studies of the 4'-TfMU modified oligonucleotides revealed that the ribose of 4'-TfMU was constrained in the South conformation,which was corroborated by the biochemical properties of the 4'-TfMU modified oligonucleotide,such as their affinity to complementary strands and transesterification kinetics.The South-constrained conformation,together with the intense 19F NMR signal of the 4'-TfMU makes it an ideal probe for studying the structure and function of RNA.