Chem. J. Chinese Universities ›› 2010, Vol. 31 ›› Issue (1): 88.

• Articles • Previous Articles     Next Articles

Activity Assay and Mechanism Study of Bisphosphonates as Matrix Metalloproteinase Inhibitors

LIU Xing-Chen1, LI Hong-Wei1, WANG Ye2, JIANG Kun2, FANG Xue-Xun2, WU Yu-Qing1*   

  1. 1. State Key Laboratory of Supramolecular Structure and Materials, Jilin University, Changchun 130012, China;
    2. Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, Jilin University, Changchun 130021, China
  • Received:2008-12-19 Online:2010-01-10 Published:2010-01-10
  • Contact: WU Yu-Qing. E-mail: yqwu@jlu.edu.cn
  • Supported by:

    国家自然科学基金(批准号: 20973073, 20773051)、国家“九七三”计划项目(批准号: 2007CB808006)、吉林省科技发展计划项目(批准号: 20070926-01)和教育部新世纪优秀人才支持计划资助.

Abstract:

Matrix metalloproteinases(MMPs), a group of zinc-dependent metalloproteinases, are responsible for the hydrolytic breakdown of extracellular matrix. Aberrantly over expression of MMPs has been associated with much human pathology including cancer, arthritis, and heart disease etc. Therefore, the development of MMPs inhibitors to drugs has always been of great interest to scientific institutions. Bisphosphonates were reported to be a new kind of MMPs inhibitors with great potential. According to the 3-dimensional structure, 4 bisphosphonates are designed, synthesized and tested against several typical MMPs. The inhibitory activities toward MMP-2, MMP-3 and MMP-9 were tested in vitro using flourometric method. The results show micromolar-level activity and modest selectivity toward MMPs. Molecular docking study and fluorometic titration spectra were performed to reveal the recognition and inhibition mechanism between MMPs and bisphosphonates, and the binding mode between them was proposed.

Key words: Matrix metalloproteinases(MMPs); Inhibitor; Bisphosphonate; Molecular recognition; Mechanism

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