Syntheses and base-pairing properties of locked nucleic acid nucleotides containing hypoxanthine, 2,6-diaminopurine, and 2-aminopurine nucleobases
Syntheses and base-pairing properties of locked nucleic acid nucleotides containing hypoxanthine, 2,6-diaminopurine, and 2-aminopurine nucleobases
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DOI：
10.1021/jo0303923
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发表时间：
2004-05-28
影响因子：
3.6
通讯作者：
Koshkin, AA
中科院分区：
文献类型：
--
作者：
Koshkin, AA
合成含有次黄嘌呤、2，6-二氨基嘌呤和2-氨基嘌呤核碱基的第二代2 '-O，4'-C-亚甲基连接的核苷酸1-3，并通过自动化亚磷酰胺方法掺入锁核酸（LNA）寡核苷酸中。所需的亚磷酰胺单体单元通过会聚合成有效地制备。糖基供体4与次黄嘌呤和6-氯-2-氨基嘌呤立体选择性偶联，得到4 '-C-支链核苷5和17。首次开发并详细描述了将5和17转化为亚磷酰胺11、25和29的方法。含有新LNA核苷酸的LNA八聚体的杂交特性针对完美的和单错配的DNA进行评估。结合研究表明，所有LNA八聚体非常有效地杂交DNA的沃森-克里克碱基配对规则与增加的结合亲和力相比，DNA类似物。核苷酸1-3的独特性质使它们对于进一步加强LNA技术非常有用。
Second generation 2'-O,4'-C-methylene-linked nucleotides 1-3 containing hypoxanthine, 2,6-diaminopurine, and 2-aminopurine nucleobases were synthesized and incorporated into locked nucleic acid (LNA) oligonucleotides by means of the automated phosphoramidite method. The required phosphoramidite monomeric units were efficiently prepared via convergent synthesis. The glycosyl donor 4 was stereoselectively coupled with hypoxanthine and 6-chloro-2-aminopurine to give the 4'-C-branched nucleosides 5 and 17. The methods for conversion of 5 and 17 into phosphoramidites 11, 25, and 29 were developed and described in full details for the first time. Hybridization properties of LNA octamers containing the new LNA nucleotides were assessed against perfect and singly mismatched DNA. The binding studies revealed that all LNA octamers hybridize very efficiently to DNA following Watson-Crick base-pairing rules with increased binding affinity compared to the DNA analogues. The unique properties of the nucleotides 1-3 make them very useful for further strengthening of the LNA technology.