Sasaki Kiyomi, Rahman S M Abdur, Obika Satoshi, Imanishi Takeshi, Torigoe Hidetaka
Department of Applied Chemistry, Faculty of Science, Tokyo University of Science, Shinjuku-ku, Tokyo 162-8601, Japan.
Nucleic Acids Symp Ser (Oxf). 2008(52):419-20. doi: 10.1093/nass/nrn213.
We examined the effect of 2'-O,4'-C-aminomethylene bridged nucleic acid (2',4'-BNA(NC)) 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 2',4'-BNA(NC) modified TFO was significantly higher than that observed with unmodified TFO. The 2',4'-BNA(NC) modification of TFO increased the thermal stability of the pyrimidine motif triplex at neutral pH. The present results certainly support the idea that the 2',4'-BNA(NC) backbone modification of TFO could be a key chemical modification and may eventually lead to progress in therapeutic applications of the antigene strategy in vivo.
我们研究了三链形成寡核苷酸(TFO)的2'-O,4'-C-氨基亚甲基桥连核酸(2',4'-BNA(NC))主链修饰对中性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,2',4'-BNA(NC)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形成的三链。TFO的2',4'-BNA(NC)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一种观点,即TFO的2',4'-BNA(NC)主链修饰可能是一种关键的化学修饰,并最终可能推动体内反基因策略治疗应用的进展。