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高等学校化学研究 ›› 2011, Vol. 27 ›› Issue (4): 635-640.

• Articles • 上一篇    下一篇

Screening Peptide Inhibitors Using Phage Peptide Library with Isocitrate Lyase in Mycobacterium tuberculosis as Target

YIN Yu-he1, NIU Xue1, SUN Bo2, TENG Guo-sheng1, ZHAO Yun-hui1 and WU Cong-mei1*   

  1. 1. College of Chemistry and Life Science, Changchun University of Technology, Changchun 130012, P. R. China;
    2. College of Life Science, Jilin University, Changchun 130012, P. R. China
  • 收稿日期:2010-10-22 修回日期:2010-12-31 出版日期:2011-07-25 发布日期:2011-06-29
  • 通讯作者: WU Cong-mei E-mail:wucmyue@sina.com
  • 基金资助:

    Supported by the Technology Development Funds of Education Department of Jilin Province, China(No.2008110).

Screening Peptide Inhibitors Using Phage Peptide Library with Isocitrate Lyase in Mycobacterium tuberculosis as Target

YIN Yu-he1, NIU Xue1, SUN Bo2, TENG Guo-sheng1, ZHAO Yun-hui1 and WU Cong-mei1*   

  1. 1. College of Chemistry and Life Science, Changchun University of Technology, Changchun 130012, P. R. China;
    2. College of Life Science, Jilin University, Changchun 130012, P. R. China
  • Received:2010-10-22 Revised:2010-12-31 Online:2011-07-25 Published:2011-06-29
  • Contact: WU Cong-mei E-mail:wucmyue@sina.com
  • Supported by:

    Supported by the Technology Development Funds of Education Department of Jilin Province, China(No.2008110).

PDF (PC)

摘要： When devoured by macrophages, Mycobacterium tuberculosis remains persistent in macrophages and gains energy through the glyoxylate bypass to maintain its long-term existence in host cells. Therefore it is possible to stop persistent infections by interdicting the glyoxylate bypass in which the isocitrate lyase(ICL) is the key rate-limiting enzyme and a persistence factor. ICL is the target of anti-TB(TB: tubercular) drugs, which could screen ICL out and effectively inhibit the activity of ICL in Mycobacterium tuberculosis, and because of this, anti-TB drugs can be used to kill persistent Mycobacterium tuberculosis. In this study, the ICL gene of the Mycobacterium tuberculosis H37Rv was cloned successfully and recombinant protein with bioactivity was obtained through the enzyme characteristic appraisal. The specific activity of the recombined ICL is 24 μmol·mg–1 ·min–1. The recombined ICL protein was used as the target, and phages which can specifically combine to ICL were screened in the phage 7 peptide library. According to the results of the ELISA and DNA sequence detection, eventually three 7-peptide chains were synthesized. Then the peptide chains were reacted with ICL, respectively, to detect their inhibitory effects on ICL. The results show that all the three 7-peptide chains possessed varying inhibitory effects on the activity of ICL. This study provided lead compounds for the research and development of new peptide anti-TB drugs.

关键词: Mycobacterium tuberculosis, Isocitrate lyase, Gene expression, Phage peptide library, Peptide inhibitor

Abstract: When devoured by macrophages, Mycobacterium tuberculosis remains persistent in macrophages and gains energy through the glyoxylate bypass to maintain its long-term existence in host cells. Therefore it is possible to stop persistent infections by interdicting the glyoxylate bypass in which the isocitrate lyase(ICL) is the key rate-limiting enzyme and a persistence factor. ICL is the target of anti-TB(TB: tubercular) drugs, which could screen ICL out and effectively inhibit the activity of ICL in Mycobacterium tuberculosis, and because of this, anti-TB drugs can be used to kill persistent Mycobacterium tuberculosis. In this study, the ICL gene of the Mycobacterium tuberculosis H37Rv was cloned successfully and recombinant protein with bioactivity was obtained through the enzyme characteristic appraisal. The specific activity of the recombined ICL is 24 μmol·mg–1 ·min–1. The recombined ICL protein was used as the target, and phages which can specifically combine to ICL were screened in the phage 7 peptide library. According to the results of the ELISA and DNA sequence detection, eventually three 7-peptide chains were synthesized. Then the peptide chains were reacted with ICL, respectively, to detect their inhibitory effects on ICL. The results show that all the three 7-peptide chains possessed varying inhibitory effects on the activity of ICL. This study provided lead compounds for the research and development of new peptide anti-TB drugs.

Key words: Mycobacterium tuberculosis, Isocitrate lyase, Gene expression, Phage peptide library, Peptide inhibitor

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