PHOSPHOROTHIOATE-MODIFIED OLIGODEOXYRIBONUCLEOTIDES .3. NMR AND UV SPECTROSCOPIC STUDIES OF THE RP-RP, SP-SP, AND RP-SP DUPLEXES, [D(GGSAATTCC)]2, DERIVED FROM DIASTEREOMERIC O-ETHYL PHOSPHOROTHIOATES
PHOSPHOROTHIOATE-MODIFIED OLIGODEOXYRIBONUCLEOTIDES .3. NMR AND UV SPECTROSCOPIC STUDIES OF THE RP-RP, SP-SP, AND RP-SP DUPLEXES, [D(GGSAATTCC)]2, DERIVED FROM DIASTEREOMERIC O-ETHYL PHOSPHOROTHIOATES
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DOI：
10.1093/nar/14.22.9081
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发表时间：
1986-11-25
影响因子：
14.9
通讯作者：
ZON, G
中科院分区：
文献类型：
--
作者：
LAPLANCHE, LA;JAMES, TL;ZON, G
将标题寡核苷酸获得的2D-NOE和1H NMR化学位移数据与先前报道的未修饰的“母体“结构的类似数据[Broido et al.（1985）匈奴J.Biochem.150，117-128]进行比较，[d（GGAAfCC）]2。用硫取代磷酸氧所引起的光谱可检测的结构扰动主要位于GsA部分内，并且对于其中硫被定向到B-螺旋的大沟中的Rp构型而言更大。UV衍生的Tm测量给出了双链体在0.4M NaCl中的以下稳定性顺序：未修饰的（33.9±0.1 °C）sp-sp（34.1 °C）>（31.7 °C）。标题化合物通过一种新的和方便的合成路线制备，该路线利用HPLC分离非对映体的O-乙基硫代磷酸酯前体（Rp）-和（Sp）-d[GG（S，EtMe）2] CO），用于随后通过氨在水中的脱乙基化。
2D—NOE and1H NMR chemical shift data obtained for the title oligonucleotides were compared with similar data previously reported [Broido et al. (1985) Hun J. Biochem. 150, 117–128] for the unmodified “parent”structure, [d(GGAAflCC)]2. The spectroscopically detectable structural perturbations caused by replacement of phosphate oxygen with sulfur were mostly localized within the GsA moiety, and re greater for the Rpconfiguration wherein sulfur is oriented into the major groove of the B—helix. UV—derived Tmmeasurements gave the following order of stability for the duplexes in 0.4 M NaC1: unmodified (33.9±0.1 °C) sp-sp(34.1 °C) > (31.7 °C). The title compounds were prepared by a new and convenient synthetic route which utilized HPLC to separate the diastereomeric O—ethyl phosphorothioate precursors, (Rp)— and (Sp)—d[GG(S, EtMflCC), for subsequent de—ethylation by ammonia in water.