Torigoe H
Institute of Physical and Chemical Research (RIKEN), 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan.
Nucleic Acids Res Suppl. 2001(1):57-8. doi: 10.1093/nass/1.1.57.
I examined the effect of N3'-->P5' phosphoramidate (PN) backbone modification of triplex-forming oligonucleotide (TFO) on the pyrimidine motif triplex formation at neutral pH, a condition where pyrimidine motif triplexes are unstable. Both thermodynamic and kinetic analyses have indicated that the PN modification of TFO increased the binding constant of the pyrimidine motif triplex formation at pH 6.8 by nearly 2 orders of magnitude. Kinetic data have also demonstrated that the observed increase in the binding constant at neutral pH by the PN modification resulted mainly from the considerable decrease in the dissociation rate constant rather than the increase in the association rate constant. The present results certainly support the idea that the PN modification of TFO could be a key modification and may eventually lead to progress in therapeutic applications of the antigene strategy in vivo.
我研究了三链形成寡核苷酸（TFO）的N3'→P5'氨基磷酸酯（PN）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。热力学和动力学分析均表明，TFO的PN修饰使pH 6.8时嘧啶基序三链形成的结合常数增加了近2个数量级。动力学数据还表明，PN修饰在中性pH下观察到的结合常数增加主要是由于解离速率常数的显著降低，而不是缔合速率常数的增加。目前的结果确实支持这样一种观点，即TFO的PN修饰可能是一种关键修饰，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。
