標題: | Azide-alkyne cycloaddition for universal post-synthetic modifications of nucleic acids and effective synthesis of bioactive nucleic acid conjugates |
作者: | Su, Yu-Chih Lo, Yu-Lun Hwang, Chi-Ching Wang, Li-Fang Wu, Min Hui Wang, Eng-Chi Wang, Yun-Ming Wang, Tzu-Pin 生物科技學系 Department of Biological Science and Technology |
公開日期: | 2014 |
摘要: | The regioselective post-synthetic modifications of nucleic acids are essential to studies of these molecules for science and applications. Here we report a facile universal approach by harnessing versatile phosphoramidation reactions to regioselectively incorporate alkynyl/azido groups into post-synthetic nucleic acids primed with phosphate at the 5\' termini. With and without the presence of copper, the modified nucleic acids were subjected to azide-alkyne cycloaddition to afford various nucleic acid conjugates including a peptide-oligonucleotide conjugate (POC) with high yield. The POC was inoculated with human A549 cells and demonstrated excellent cell-penetrating ability despite cell deformation caused by a small amount of residual copper chelated to the POC. The combination of phosphoramidation and azide-alkyne cycloaddition reactions thus provides a universal regioselective strategy to post-synthetically modify nucleic acids. This study also explicated the toxicity of residual copper in synthesized bioconjugates destined for biological systems. |
URI: | http://hdl.handle.net/11536/25105 http://dx.doi.org/10.1039/c4ob01132e |
ISSN: | 1477-0520 |
DOI: | 10.1039/c4ob01132e |
期刊: | ORGANIC & BIOMOLECULAR CHEMISTRY |
Volume: | 12 |
Issue: | 34 |
起始頁: | 6624 |
結束頁: | 6633 |
顯示於類別: | 期刊論文 |