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Journal of Chinese Pharmaceutical Sciences ›› 2019, Vol. 28 ›› Issue (12): 825-834.DOI: 10.5246/jcps.2019.12.078

• Original articles •     Next Articles

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*   

  1. 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).

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

CLC Number: 

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