Synthesis and thermodynamic studies of oligodeoxyribonucleotides containing tandem lesions of thymidine glycol and 8-oxo-2′-deoxyguanosine
Synthesis and thermodynamic studies of oligodeoxyribonucleotides containing tandem lesions of thymidine glycol and 8-oxo-2′-deoxyguanosine
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DOI：
10.1021/tx060032l
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发表时间：
2006-06-19
影响因子：
4.1
通讯作者：
Wang, Yinsheng
中科院分区：
文献类型：
--
作者：
Wang, Yuesong;Wang, Yinsheng
胸苷二醇（Tg），也称为5,6-二羟基-5,6-二氢胸苷和8-氧代-7,8-二氢-2'-脱氧鸟苷（8-oxodG）是活性氧（ROS）诱导的两种主要DNA损伤产物。在这里，我们报道了含有 Tg 和 8-oxodG 的寡脱氧核糖核苷酸 (ODN) 的合成。两个单碱基损伤的双重掺入是通过使用具有超温和碱基保护基团的 8-oxodG 亚磷酰胺结构单元和核碱基羟基受到乙酰基官能团保护的 Tg 结构单元来实现的。携带邻近 8-oxodG 和 Tg 的 ODN 的可用性为评估这种串联损伤的形成和检查复制和修复提供了可靠的底物。此外，从熔化温度数据得出的热力学参数表明，串联损伤比单独的两个单碱基损伤中的任何一个都更大程度地破坏双螺旋的稳定性。热力学结果可以为理解串联基底损伤的修复提供基础。
Thymidine glycol (Tg), which is also known as 5,6-dihydroxy-5,6-dihydrothymidine, and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) are two major types of DNA damage products induced by reactive oxygen species (ROS). Here, we report the synthesis of oligodeoxyribonucleotides (ODNs) containing both Tg and 8-oxodG. The dual incorporation of the two single-base lesions was achieved by using a phosphoramidite building block of 8-oxodG with ultramild base protecting group and a building block of Tg whose nucleobase hydroxyl groups were protected with acetyl functionality. The availability of ODNs carrying neighboring 8-oxodG and Tg provided authentic substrates for assessing the formation and examining the replication and repair of this kind of tandem lesions. In addition, thermodynamic parameters derived from melting temperature data revealed that tandem lesions destabilized the double helix to a greater extent than either of the two single-base lesions alone. The thermodynamic results could offer a basis for understanding the repair of the tandem base lesions.