Torigoe Hidetaka, Kawahashi Kouji, Tamura Yusuke
Department of Applied Chemistry, Faculty of Science, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan.
Nucleic Acids Res Suppl. 2003(3):157-8. doi: 10.1093/nass/3.1.157.
We examined the effect of morpholino (MOR) 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 MOR-modified TFO was approximately 60 times larger than that observed with unmodified TFO. Kinetic data demonstrated that the observed increase in the binding constant at neutral pH by the MOR backbone modification resulted mainly from the considerable increase in the association rate constant. The present results certainly support the idea that the MOR backbone modification of TFO could be a key 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）的吗啉代（MOR）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，MOR修饰的TFO形成嘧啶基序三链的结合常数比未修饰的TFO大约60倍。动力学数据表明，MOR主链修饰导致中性pH下结合常数增加，这主要是由于缔合速率常数显著增加。目前的结果确实支持这样的观点，即TFO的MOR主链修饰可能是一种关键修饰，并最终可能推动体内反基因策略治疗应用的进展。
