Design, Synthesis and Biological Activity of Novel Chemical Modified siRNAs

Chin. J. Org. Chem. ›› 2010, Vol. 30 ›› Issue (12): 1865-1869. Previous Articles Next Articles

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新型化学修饰siRNAs的设计、合成及生物活性研究

李祎亮¹^{,2，任开环¹，李洪明³，王菊仙¹，邹美香²，何红伟¹，邵荣光¹，王玉成*^,1}

(¹中国医学科学院医药生物技术所北京 100050)
(²天津药物研究院天津市新药设计与发现重点实验室天津 300193)
(³天津中医药大学天津 300193)

收稿日期:2010-02-10 修回日期:2010-05-08 发布日期:2010-07-19
通讯作者: 李祎亮 E-mail:langyil@sina.com
基金资助:
“重大新药创制”科技重大专项分项目

Design, Synthesis and Biological Activity of Novel Chemical Modified siRNAs

Li Yiliang¹,2 Ren Kaihuan¹ Li Hong-ming³ Wang Juxian¹ Zou Meixiang² He Hongwei¹ Shao Rongguang¹ Wang Yucheng*^,1

(¹Institute of Medicinal Biotechnology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100050)
(²Tianjin Key Laboratory of Molecular Design & Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193)
(³Tianjin University of Traditional Chinese Medical, Tianjin 300193)

Received:2010-02-10 Revised:2010-05-08 Published:2010-07-19

Abstract

Four aromatic chemically modified units were synthesized by multi-step reactions from substituted phenol and 3-chloro-1,2-epoxypropane. These compounds were incorporated into the 3 -overhang regions of siRNAs targeting mdm2 mRNA to prepare nine modified siRNA molecules. The antitumor activity of the synthesized siRNAs was evaluated by methylthiazolyl tetrazolium (MTT) method. The nuclease stability of the individual siRNAs was tested in vitro. Based on the preliminary experimental results and com-pared with the natural siRNA, three modified siRNA molecules (siRNA8, siRNA11 and siRNA15) showed remarkable improvement in bioactivity and stability. siRNA11 was shown to be 2-fold more potent and 10-fold increase in half-time of nuclease resistance.

Key words: chemical modification, siRNA, anticancer activity

Cite this article

LI Yi-Liang, REN Kai-Huan, LI Hong-Ming, WANG Ju-Xian, ZOU Mei-Xiang, HE Hong-Wei, SHAO Rong-Guang, WANG Yu-Cheng. Design, Synthesis and Biological Activity of Novel Chemical Modified siRNAs[J]. Chin. J. Org. Chem., 2010, 30(12): 1865-1869.

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新型化学修饰siRNAs的设计、合成及生物活性研究

Design, Synthesis and Biological Activity of Novel Chemical Modified siRNAs

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