Proton nuclear magnetic resonance studies on dideoxyribonucleoside methylphosphonates.
Proton nuclear magnetic resonance studies on dideoxyribonucleoside methylphosphonates.
复制标题
双脱氧核糖核苷甲基膦酸酯的质子核磁共振研究。
DOI：
10.1021/bi00551a020
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发表时间：
1980
期刊：
影响因子：
2.9
通讯作者：
P. O. Ts'o
中科院分区：
文献类型：
--
作者：
Lou;Doris M. Cheng;Paul S. Miller;Junichi Yano;P. O. Ts'o
化学合成了一系列双脱氧核糖核苷甲基膦酸酯，d-ApA、d-ApT、d-TpA 和 TpT，并分离了每个二聚体的非对映异构体 [Miller, P. S., Yano, J., Yano, E., Carroll, C., Jayaraman, K., & Ts'o, P. O. P. (1979) Biochemistry 18、 5134]。这些化合物的 1H NMR 谱与其母体二酯化合物的谱相似。具体而言，通过与未修饰的亲本 d-ApA 进行比较，再次确认了 d-ApA 的两种非对映异构体（指定为 1 和 2）的 1H 共振归属。通过 NOE 技术测定了两种异构体 (d-ApA)1 和 (d-ApA)2 的膦酸甲基的绝对构型。通过光谱模拟技术对d-ApA非对映异构体以及相应的单体组分dAp和CH3pdA以及TpT的1H NMR谱进行了分析。因此，可以精确测定脱氧呋喃核糖环和膦酸甲基的质子共振的所有耦合常数和化学位移。这些数据为分析这些新型非离子核酸类似物的糖褶皱和主链构象提供了信息。研究发现，每种异构体的糖-磷酸骨架的构象彼此相似，并且与母体二核苷单磷酸的构象相似。 (d-ApA)1 和 (d-ApA)2 的平均腺嘌呤堆积构象以计算机分析得出的数字坐标进行描述，其中包括环流磁各向异性和原子抗磁各向异性效应。这两个计算机导出的构象模型与仅基于环电流效应的图形近似导出的模型相似。对于每对二聚体类似物，异构体1的碱基堆积模式与其母体二酯相似，而异构体2的碱基重叠程度小于异构体1。基于NMR数据的构象分析结果与这些二聚体的紫外和圆二色性测量获得的结果一致。
A series of dideoxyribonucleoside methylphosphonates, d-ApA, d-ApT, d-TpA, and TpT, were synthesized chemically and the diastereoisomers of each dimer were separated [Miller, P. S., Yano, J., Yano, E., Carroll, C., Jayaraman, K., & Ts'o, P. O. P. (1979) Biochemistry 18, 5134]. The 1H NMR spectra of these compounds are similar to those of their parent diester compounds. Specifically, the assignments of the 1H resonances of the two diastereoisomers of d-ApA (designated as 1 and 2) were reaffirmed by comparing with the unmodified, parent d-ApA. The absolute configuration of the phosphonate methyl group of the two isomers (d-ApA)1 and (d-ApA)2 was determined by the NOE technique. The 1H NMR spectra of the diastereoisomers of d-ApA, as well as the corresponding monomer components dAp and CH3pdA, and TpT were analyzed by spectrum simulation techniques. Thus, all the coupling constants and chemical shifts of the proton resonances of the deoxyribofuranose ring and the phosphonate methyl group could be precisely determined. These data provide the information for an analysis of the sugar puckering and backbone conformations of these novel nonionic nucleic acid analogues. It was found that the conformations of the sugar-phosphate backbones of each isomer are similar to each other and are similar to the conformations of the parent dinucleoside monophosphates. The average adenine stacking conformations of (d-ApA)1 and (d-ApA)2 were described in numerical coordinates derived from a computer analysis which included both ring-current magnetic anisotropy and atomic diamagnetic anisotropy effects. The two computer-derived conformational models are similar to those derived from the graphic approximation based only on the ring-current effects. For each pair of dimer analogues, the base stacking mode of isomer 1 is similar to that of its parent diester while the extent of base overlap in isomer 2 is less than that in isomer 1. The results of the conformational analysis based on NMR data are consistent with the results obtained from ultraviolet and circular dichroism measurements on these dimers.