Triplex- and Duplex-Forming Abilities of Oligonucleotides Containing 2′-Deoxy-5-trifluoromethyluridine and 2′-Deoxy-5-trifluoromethylcytidine
Triplex- and Duplex-Forming Abilities of Oligonucleotides Containing 2′-Deoxy-5-trifluoromethyluridine and 2′-Deoxy-5-trifluoromethylcytidine
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DOI：
10.1248/cpb.c17-00530
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发表时间：
2017-10-01
影响因子：
1.7
通讯作者：
Hari, Yoshiyuki
中科院分区：
文献类型：
--
作者：
Ito, Yuta;Matsuo, Misaki;Hari, Yoshiyuki
以市售的2'-脱氧尿嘧啶和2'-脱氧-5-三氟甲基胞苷为原料，分别合成了2'-脱氧-5-三氟甲基尿嘧啶和2'-脱氧-5-三氟甲基胞苷磷酰胺。将得到的磷酰胺结合到寡核苷酸中，通过紫外熔融实验评估其与双链DNA （dsDNA）和单链RNA （ssRNA）的结合亲和力。包括5-三氟甲基嘧啶核碱基在内的寡核苷酸与dsDNA形成三联体的能力下降。特别是含有三氟甲基胞嘧啶(C-CF3)-GC碱基三重体的三重体的稳定性较低，可能是由于吸电子的三氟甲基使C-CF3质子化的pK(a)较低。仅观察到包括5-三氟甲基嘧啶核碱基在内的寡核苷酸与ssRNA形成的双链的稳定性略有下降，这表明它们可能适用于利用氟原子特征的各种ssRNA靶向技术。
A facile synthesis of 2'-deoxy-5-trifluoromethyluridine and 2'-deoxy-5-trifluoromethylcytidine phosphoramidites from commercially available 2'-deoxyuridine and 2'-deoxycytidine was achieved, respectively. The obtained phosphoramidites were incorporated into oligonucleotides, and their binding affinity to double stranded DNA (dsDNA) and single-stranded RNA (ssRNA) was evaluated by UV-melting experiments. The triplex-forming abilities of oligonucleotides including 5-trifluoromethylpyrimidine nucleobases with dsDNA were decreased. Especially, the stability of the triplex containing a trifluoromethylcytosine (C-CF3)-GC base triplet was low, likely due to the low pK(a) of protonated C-CF3 by the electron-withdrawing trifluoromethyl group. A slight decrease in stability of the duplex formed with ssRNA by oligonucleotides including 5-trifluoromethylpyrimidine nucleobases was only observed, suggesting that they might be applicable to various ssRNA-targeted technologies using features of fluorine atoms.