期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 64, 期 1, 页码 711-718出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.0c01711
关键词
-
资金
- Japan Society for the Promotion of Science KAKENHI [17H03091, 20K15402]
- Naito Foundation
- Ichiro Kanehara Foundation
- Grants-in-Aid for Scientific Research [20K15402, 17H03091] Funding Source: KAKEN
In this study, the incorporation of 8-trifluoromethyl-2'-deoxyguanosine ((F)G) into a thrombin binding aptamer (TBA) significantly increased the melting temperature and anticoagulant activity of the TBA sequence, demonstrating that (F)G is a powerful nucleoside derivative.
In this study, we incorporated 8-trifluoromethyl-2'-deoxyguanosine ((F)G) into a thrombin binding aptamer (TBA ). Circular dichroism, nuclear magnetic resonance (NMR), electrophoresis, and prothrombin time (PT) assay were performed to investigate the structure, thermodynamic stability, biological stability, and anticoagulant activity of the (F)G-modified TBA sequences. We found that the replacement of (F)G into TBA sequences led to a remarkable improvement in the melting temperature up to 30 degrees C compared with the native sequence. The trifluoromethyl group allowed us to investigate the TBA G-quadruplex structure by F-19 NMR spectroscopy. Furthermore, PT assays showed that the modified sequences can significantly improve the anticoagulant activity in comparison with the native TBA. Finally, we demonstrated that the trifluoromethyl-modified TBA sequence could function as an anticoagulant reagent in live rats. Our results strongly suggested that (F)G is a powerful nucleoside derivative to increase the thermodynamic stability and anticoagulant activity of TBA.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据