A Sensitive Multispectroscopic Probe for Nucleic Acids
A Sensitive Multispectroscopic Probe for Nucleic Acids
复制标题
DOI：
10.1021/jp101367s
复制
发表时间：
2010-06-17
影响因子：
3.3
通讯作者：
Brewer, Scott H.
中科院分区：
文献类型：
--
作者：
Gai, Xin Sonia;Fenlon, Edward E.;Brewer, Scott H.
叠氮化合物最近被用作蛋白质的振动探针，但它们在核酸中的结合仅限于光交联或点击化学应用。研究了2‘-叠氮-2’-脱氧尿苷(N-3-DU，1)作为核酸糖磷酸主链区域红外和核磁共振光谱探针的可行性，考察了溶剂、异二聚体形成和温度对谱峰频率和红外光谱带宽的影响。N-3-DU的叠氮红外不对称伸缩带(Nu)对环境很敏感，从THF到水时发生了13.5 cm(-1)的蓝移。研究了溶剂对叠氮基团中每个氮原子的N-15化学位移(15N)的影响，其中末端氮原子对溶剂最敏感，当溶剂从THF-d(8)改为D2O时，其下场移动了3.8ppm。在氯仿中，3(硅醚类似物1)和2，6-二庚胺基吡啶(4)之间形成的碱基对状杂二聚体分别导致IR和N-15核磁共振光谱频率和化学位移的微小变化，正如预期的那样，给定叠氮部分的位置。在所研究的温度范围内，(Nu)相对于Tide(N3)和Delta(15N)的本征温度依赖性被发现是最小的，特别是与这些光谱观测值的溶剂依赖性相比。对模型体系的密度泛函理论(DFT)计算补充了实验研究的分析。
Azides have recently been used as vibrational probes of proteins, but their incorporation into nucleic acids has been limited to photo-cross-linking or click chemistry applications. The utility of 2'-azido-2'-deoxyuridine (N-3-dU, 1) as an IR and N-15 NMR spectroscopic probe of the sugar phosphate backbone region of nucleic acids was investigated by measuring the effects of solvent, heterodimer formation, and temperature on peak frequencies and IR bandwidth. The azide IR asymmetric stretching band ((nu) over tilde (N3)) of N-3-dU was sensitive to its environment, undergoing a blue shift of 13.5 cm(-1) when changing the solvent from THF to water. The solvent effects on N-15 chemical shifts (delta(15N)) of each of the nitrogen atoms in the azido group was studied, and the terminal nitrogen atom was the most sensitive to solvent, shifting downfield by 3.8 ppm when changing the solvent from THF-d(8) to D2O. Formation of a base-pair-like heterodimer between 3 (a silyl ether analogue of 1) and 2,6-diheptanamidopyridine (4) in chloroform resulted in minimal changes in the IR and N-15 NMR spectral frequency and chemical shift, respectively, as expected given the location of the azido moiety. The intrinsic temperature dependence of (nu) over tilde (N3) and delta(15N) were found to be minimal over the temperature range studied especially compared to the solvent dependence of these spectral observables. The analysis of the experimental studies was complemented by density functional theory (DFT) calculations on model systems.