C5-Alkynyl-Functionalized 伪-L-LNA: Synthesis, Thermal Denaturation Experiments and Enzymatic Stability

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• 作者：Pawan Kumar ; Bharat Baral ; Brooke A. Anderson ; Dale C. Guenther ; Michael E. 脴stergaard ; Pawan K. Sharma ; Patrick J. Hrdlicka
• 刊名：Journal of Organic Chemistry
• 出版年：2014
• 出版时间：June 6, 2014
• 年：2014
• 卷：79
• 期：11
• 页码：5062-5073
• 全文大小：488K
• 年卷期：v.79,no.11(June 6, 2014)
• ISSN：1520-6904

文摘

Major efforts are currently being devoted to improving the binding affinity, target specificity, and enzymatic stability of oligonucleotides used for nucleic acid targeting applications in molecular biology, biotechnology, and medicinal chemistry. One of the most popular strategies toward this end has been to introduce additional modifications to the sugar ring of affinity-inducing conformationally restricted nucleotide building blocks such as locked nucleic acid (LNA). In the preceding article in this issue, we introduced a different strategy toward this end, i.e., C5-functionalization of LNA uridines. In the present article, we extend this strategy to 伪-L-LNA: i.e., one of the most interesting diastereomers of LNA. 伪-L-LNA uridine monomers that are conjugated to small C5-alkynyl substituents induce significant improvements in target affinity, binding specificity, and enzymatic stability relative to conventional 伪-L-LNA. The results from the back-to-back articles therefore suggest that C5-functionalization of pyrimidines is a general and synthetically straightforward approach to modulate biophysical properties of oligonucleotides modified with LNA or other conformationally restricted monomers.