Development of oligonucleotide-based antagonists of Ebola virus protein 24 inhibiting its interaction with karyopherin alpha 1
Development of oligonucleotide-based antagonists of Ebola virus protein 24 inhibiting its interaction with karyopherin alpha 1
复制标题
开发基于寡核苷酸的埃博拉病毒蛋白 24 拮抗剂，抑制其与核转运蛋白 α 1 的相互作用
DOI：
10.1039/c8ob00706c
复制
发表时间：
2018
影响因子：
3.2
通讯作者：
Obika Satoshi
中科院分区：
文献类型：
--
作者：
Tanaka Keisuke;Kasahara Yuuya;Miyamoto Yoichi;Takumi Okuda;Kasai Tatsuro;Onodera Kentaro;Kuwahara Masayasu;Oka Masahiro;Yoneda Yoshihiro;Obika Satoshi
蛋白质-蛋白质相互作用（PPI）的研究和拮抗剂的制备对于确定某些蛋白质是否是合适的医学靶标非常重要。在本研究中，我们使用的毛细管电泳系统进化的配体指数富集产生天然和人工核酸适体靶向埃博拉病毒蛋白24（eVP 24），证明人工适体，利用合成的尿苷类似物与腺嘌呤残基在其C5位置，表现出超过天然的活动。为了证实所制备的适体的功能，通过毛细管电泳和生物层干涉法测定它们抑制eVP 24的PPI的能力，并且所获得的结果明确地证明这些适体与eVP 24的功能位点相互作用，因此是良好的拮抗剂。
The investigation of protein–protein interactions (PPIs) and the preparation of antagonists are important for determining whether certain proteins are suitable medical targets. In the present study, we used the capillary electrophoresis-systematic evolution of ligands by exponential enrichment to generate natural and artificial nucleic acid aptamers targeting Ebola virus protein 24 (eVP24), demonstrating that artificial aptamers, synthesised utilising a uridine analogue with an adenine residue at its C5 position, exhibited activities exceeding those of natural ones. To confirm the functionality of the as-prepared aptamers, their abilities to inhibit the PPIs of eVP24 were determined by capillary electrophoresis and bio-layer interferometry, and the obtained results unambiguously demonstrated that these aptamers interacted with the functional site of eVP24 and were thus good antagonists.