Pozmogova G E, Zaitseva M A, Smirnov I P, Shvachko A G, Murina M A, Sergeenko V I
Bioengineering Center, the Russian Academy of Sciences, Moscow, Russia.
Bull Exp Biol Med. 2010 Dec;150(2):180-4. doi: 10.1007/s10517-010-1099-5.
In order to create effective therapeutically significant oligonucleotide structures, a series of analogs of thrombin-binding aptamer d(GGTTGGTGTGGTTGG) containing thiophosphoryl substitutions were synthesized. The anticoagulation effects of the resultant thrombin-binding aptamer analogs were evaluated and the effects of local thiomodifications on their structure and function were studied, including the effects on stability in blood plasma and resistance to DNA nucleases. A promising modified oligonucleotide (LL11) was found with the structure modified only in TT loops. It retains antithrombin properties of thrombin-binding aptamer, but is more resistant to biodegradation.
为了创建具有显著治疗效果的寡核苷酸结构，合成了一系列含有硫代磷酸取代的凝血酶结合适体d(GGTTGGTGTGGTTGG)类似物。评估了所得凝血酶结合适体类似物的抗凝作用，并研究了局部硫代修饰对其结构和功能的影响，包括对血浆稳定性和对DNA核酸酶抗性的影响。发现了一种有前景的修饰寡核苷酸(LL11)，其结构仅在TT环处进行了修饰。它保留了凝血酶结合适体的抗凝血特性，但对生物降解更具抗性。
