无环鸟苷修饰的环二鸟苷酸合成及其诱导I型干扰素释放活性评价

doi:10.5246/jcps.2019.12.078

中国药学(英文版) ›› 2019, Vol. 28 ›› Issue (12): 825-834.DOI: 10.5246/jcps.2019.12.078

• 【研究论文】 • 下一篇

无环鸟苷修饰的环二鸟苷酸合成及其诱导I型干扰素释放活性评价

代宏, 于小桐, 关注, 张礼和, 杨振军^*

北京大学医学部药学院天然药物及仿生药物国家重点实验室, 北京 100191

收稿日期:2019-06-27 修回日期:2019-09-20 出版日期:2019-12-28 发布日期:2019-10-25
通讯作者: Tel.: +86-10-82802503, E-mail: yangzj@bjmu.edu.cn
基金资助:
National Natural Science Foundation of China (Grant No. U1604285, 21572013).

Synthesis of c-di-GMP analogs modified by ganciclovir and biological activity to induce type I interferon

Hong Dai, Xiaotong Yu, Zhu Guan, Lihe Zhang, Zhenjun Yang^*

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2019-06-27 Revised:2019-09-20 Online:2019-12-28 Published:2019-10-25
Contact: Tel.: +86-10-82802503, E-mail: yangzj@bjmu.edu.cn
Supported by:
National Natural Science Foundation of China (Grant No. U1604285, 21572013).

摘要/Abstract

摘要：

环二鸟苷酸(c-di-GMP)是一种重要的第二信使,其不仅参与调控多种细菌生理活动,还能够激活哺乳动物天然免疫信号通路诱导I型干扰素等的释放。本文报道了利用亚磷酰胺一釜环合法,合成了无环鸟苷修饰的c-di-GMP及其磷硫代类似物(7a, 7b, 7c), 发现其诱导小鼠巨噬细胞释放I型干扰素的活性完全丧失,表明c-di-GMP的糖环结构对其保持激活STING信号通路的能力至关重要。

关键词: 环二核苷酸, c-di-GMP衍生物, 丙环鸟苷, I型干扰素

Abstract:

C-di-GMP is one kind of second messengers which plays an important role not only in the regulation of various bacterialphysiological activities but also in the activation of innate immune response to induce type I interferon in mammalian cells. In thisassay, by using one-pot phosphoramidite method, three novel kinds of analogs of c-di-GMP including its phosphorthiates modified by ganciclovir (7a, 7b, 7c) have been designed and synthesized. The immune-stimulatory results of these c-di-GMP analogs in RAW-Lucia ISG cells indicated that they couldn’t induce the release of type I interferon, which demonstrated that the intact structure of ribose moieties is very vital for their bioactivity upon the activation of STING signaling pathway.

Key words: Cyclic dinucleotides, c-di-GMP analogs, Ganciclovir, Type I interferon

中图分类号:

R914

Supporting:

代宏, 于小桐, 关注, 张礼和, 杨振军. 无环鸟苷修饰的环二鸟苷酸合成及其诱导I型干扰素释放活性评价[J]. 中国药学(英文版), 2019, 28(12): 825-834.

Hong Dai, Xiaotong Yu, Zhu Guan, Lihe Zhang, Zhenjun Yang. Synthesis of c-di-GMP analogs modified by ganciclovir and biological activity to induce type I interferon[J]. Journal of Chinese Pharmaceutical Sciences, 2019, 28(12): 825-834.

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无环鸟苷修饰的环二鸟苷酸合成及其诱导I型干扰素释放活性评价

Synthesis of c-di-GMP analogs modified by ganciclovir and biological activity to induce type I interferon

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