通过3'-氨基-2'-O,4'-C-亚甲基桥连核酸修饰促进三链体形成。

Promotion of triplex formation by 3'-amino-2'-O,4'-C-methylene bridged nucleic acid modification.

作者信息

Sasaki Kiyomi, Rahman S M Abdur, Sato Norihiro, Obika Satoshi, Imanishi Takeshi, Torigoe Hidetaka

机构信息

Department of Applied Chemistry, Faculty of Sciecne, Tokyo University of Science, Tokyo 162-8601, Japan.

出版信息

Nucleic Acids Symp Ser (Oxf). 2009(53):159-60. doi: 10.1093/nass/nrp080.

DOI:10.1093/nass/nrp080

PMID:19749309

Abstract

We examined the effect of 3'-amino-2'-O,4'-C-methylene bridged nucleic acid (3'-amino-2',4'-BNA) backbone modification of triplex-forming oligonucleotide (TFO) on the pyrimidine motif triplex formation at neutral pH, a condition where pyrimidine motif triplexes are unstable. The melting temperature of the pyrimidine motif triplex at pH 6.8 with 3'-amino-2',4'-BNA modified TFO was significantly higher than that observed with unmodified TFO. The 3'-amino-2',4'-BNA modification of TFO increased the thermal stability of the pyrimidine motif triplex at neutral pH. The present results certainly support the idea that the 3'-amino-2',4'-BNA modification of TFO could be a key chemical modification and may eventually lead to progress in therapeutic applications of the antigene strategy in vivo.

摘要

我们研究了三链形成寡核苷酸（TFO）的3'-氨基-2'-O，4'-C-亚甲基桥连核酸（3'-氨基-2'，4'-BNA）骨架修饰对中性pH条件下嘧啶基序三链形成的影响，在该条件下嘧啶基序三链不稳定。在pH 6.8时，3'-氨基-2'，4'-BNA修饰的TFO形成的嘧啶基序三链的解链温度显著高于未修饰TFO所观察到的解链温度。TFO的3'-氨基-2'，4'-BNA修饰提高了中性pH条件下嘧啶基序三链的热稳定性。目前的结果确实支持这样的观点，即TFO的3'-氨基-2'，4'-BNA修饰可能是一种关键的化学修饰，并最终可能推动反基因策略在体内治疗应用方面取得进展。