Synthesis and properties of oligodeoxynucleotides incorporating a conformationally rigid uridine unit having a cyclic structure at the 5'-terminal site.
Synthesis and properties of oligodeoxynucleotides incorporating a conformationally rigid uridine unit having a cyclic structure at the 5'-terminal site.
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掺入在 5-末端位点具有环状结构的构象刚性尿苷单元的寡脱氧核苷酸的合成和性质。
DOI：
10.1002/chin.200042202
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Takeshi Wada
中科院分区：
文献类型：
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作者：
M. Sekine;Osamu Kurasawa;K. Shohda;K. Seio;Takeshi Wada
合成了在尿嘧啶残基的5位和5 ′-磷酸基之间连接有环状结构的2 ′-O-甲基尿苷酸衍生物3。NMR分析表明，该环尿苷酸衍生物具有唯一的C3 '-内构象，其有利于与RNA形成双链体。两种寡核苷酸？通过在固相合成中使用完全保护的环尿苷酸3 ′-亚磷酰胺衍生物11，合成了在5 ′-末端位点引入该环尿苷酸单元的pc 3Um（pT）（9）和pc 3Um（pU）（9）。为了研究这种环状结构对修饰的寡核苷酸和它们的互补寡核苷酸之间的双链体的热稳定性的实际影响，还合成了具有非环状结构的两种寡核苷酸pUm（pT）（9）和pUm（pU）（9）。作为互补寡核苷酸，dA（pdA）（9）和A（pA）（9）用于这些5 ′-末端修饰寡核苷酸的T（m）实验。测量所有可能的双链体的T（m）值。这些结果清楚地表明，pc 3Um（pT）（9）-A（pA）（9）的双链体具有比A（pA）（9）-T（pT）（9）高5.5 ℃的T（m）值。与其他所有情况相比，这是相当重要的。此外，pc 3Um（pT）（9）-A（pA）（9）的T（m）值比pUm（pT）（9）-A（pA）（9）的T（m）值高4.5 ℃。该结果表明，环状结构仅在修饰的寡聚体（DNA）和十腺苷酸（RNA）的情况下对双链体的稳定性有显著贡献。
A 2'-O-methyluridylic acid derivative 3 having a cyclic structure linked between the 5-position of the uracil residue and the 5'-phosphate group was synthesized. The NMR analysis suggests that this cyclouridylic acid derivative has exclusively the C3'-endo conformation that is in favor of duplex formation with RNA. Two oligonucleotides ¿pc3Um(pT)(9) and pc3Um(pU)(9) incorporating this cyclouridylic acid unit at the 5'-terminal site were synthesized by using the fully protected cyclouridylic acid 3'-phosphoramidite derivative 11 in the solid-phase synthesis. To examine the actual effect of this cyclic structure on the thermal stability of duplexes between the modified oligonucleotides and their complementary oligonucleotides, two oligonucleotides ¿pUm(pT)(9) and pUm(pU)(9) having an acyclic structure were also synthesized. As the complementary oligonucleotides, dA(pdA)(9) and A(pA)(9) were used for T(m) experiments with these 5'-terminal modified oligonucleotides. The T(m) values of all the possible duplexes were measured. These results clearly show that the duplex of pc3Um(pT)(9)-A(pA)(9) has a higher T(m) value by 5.5 degrees C than that of A(pA)(9)-T(pT)(9). This is rather significant compared with all other cases. Moreover, the T(m) value of pc3Um(pT)(9)-A(pA)(9) is 4.5 degrees C higher than that of pUm(pT)(9)-A(pA)(9). This result suggests that the cyclic structure can considerably contribute to stabilization of the duplex only in the case of the modified oligomer (DNA) and decaadenylate (RNA).