Sekiguchi Mitsuaki, Obika Satoshi, Somjing Roonjang, Imanishi Takeshi
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
Nucleic Acids Symp Ser (Oxf). 2004(48):7-8. doi: 10.1093/nass/48.1.7.
We have designed and successfully synthesized a novel bridged nucleic acid analogue with a P3'-->N5' phosphoramidate linkage, 5'-amino-3',5'-BNA. X-ray crystallographic analysis demonstrated that the 5'-amino-3',5'-BNA had C1-exo-O4-endo sugar puckering and a constrained gamma dihedral angle of 22.8 degrees. The oligonucleotides containing 5'-amino-3',5'-BNA exhibited strong binding affinity towards complementary strands. In addition, the 5'-amino-3',5'-BNA oligonucleotide was easily hydrolyzed at its phosphoramidate linkage under mild acidic conditions.
我们设计并成功合成了一种具有P3'→N5'氨基磷酸酯键的新型桥连核酸类似物，即5'-氨基-3',5'-BNA。X射线晶体学分析表明，5'-氨基-3',5'-BNA具有C1-外向-O4-内向糖折叠构象，且γ二面角受限为22.8度。含有5'-氨基-3',5'-BNA的寡核苷酸对互补链表现出很强的结合亲和力。此外，5'-氨基-3',5'-BNA寡核苷酸在温和酸性条件下易在其氨基磷酸酯键处发生水解。
