Department of Engineering Science, Graduate School of Informatics and Engineering, University of Electro-Communications (UEC), Chofu 182-8585, Japan.
School of Medicine and Public Health, University of Wisconsin, Madison, WL 53706, USA.
Int J Mol Sci. 2022 Jul 14;23(14):7778. doi: 10.3390/ijms23147778.
A major obstacle to the therapeutic application of an aptamer is its susceptibility to nuclease digestion. Here, we confirmed the acquisition of relative nuclease resistance of a DNA-type thrombin binding aptamer with a warhead (TBA) by covalent binding to a target protein in the presence of serum/various nucleases. When the thrombin-inhibitory activity of TBA on thrombin was reversed by the addition of the complementary strand, the aptamer was instantly degraded by the nucleases, showing that the properly folded/bound aptamer conferred the resistance. Covalently binding aptamers possessing both a prolonged drug effect and relative nuclease resistance would be beneficial for in vivo translational applications.
一种适体在治疗应用上面临的一个主要障碍是其对核酸酶消化的敏感性。在这里，我们在血清/各种核酸酶存在的情况下通过与靶蛋白共价结合，证实了带有弹头（TBA）的 DNA 型凝血酶结合适体获得了相对的核酸酶抗性。当互补链的加入逆转 TBA 对凝血酶的抑制活性时，适体立即被核酸酶降解，表明适当折叠/结合的适体赋予了抗性。共价结合的具有延长药物作用和相对核酸酶抗性的适体将有利于体内转化应用。
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