Torigoe Hidetaka, Nagasawa Nobuyuki
Department of Applied Chemistry, Faculty of Science, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan.
Nucleic Acids Symp Ser (Oxf). 2007(51):161-2. doi: 10.1093/nass/nrm081.
We examined the effect of 2'-O,4'-C-ethylene bridged nucleic acid (ENA) 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 binding constant of the pyrimidine motif triplex formation at pH 6.8 with ENA-modified TFO was 20 times larger than that observed with unmodified TFO. The number and position of the ENA modification introduced into the TFO did not significantly affect the magnitude of the increase in the binding constant. The consideration of the observed thermodynamic parameters suggested that the increased rigidity itself of the ENA-modified TFO in the free state relative to the unmodified TFO may enable the significant increase in the binding constant at neutral pH. The present results certainly support the idea that the ENA 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-乙烯桥连核酸（ENA）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是不稳定的。在pH 6.8时，ENA修饰的TFO形成嘧啶基序三链的结合常数比未修饰的TFO观察到的结合常数大20倍。引入TFO中的ENA修饰的数量和位置对结合常数增加的幅度没有显著影响。对观察到的热力学参数的考虑表明，相对于未修饰的TFO，ENA修饰的TFO在自由状态下增加的刚性本身可能使中性pH下的结合常数显著增加。目前的结果肯定支持这样的观点，即TFO的ENA主链修饰可能是一种关键的化学修饰，并最终可能导致体内抗原策略治疗应用的进展。
