CAJ | 학술논문

根据基质金属蛋白酶(MMPs)的活性位点附近三维空间结构, 设计合成了4种双膦酸类化合物, 利用酶促反应动力学方法对比测试了双膦酸化合物及阿伦磷酸钠(Alendronate)对MMPs的抑制效果;结合分子对接方法以及荧光滴定光谱研究了双膦酸化合物与MMPs的分子识别和作用机理, 并得到了二者的结合模型.
근거기질금속단백매(MMPs)적활성위점부근삼유공간결구, 설계합성료4충쌍련산류화합물, 이용매촉반응동역학방법대비측시료쌍련산화합물급아륜린산납(Alendronate)대MMPs적억제효과;결합분자대접방법이급형광적정광보연구료쌍련산화합물여MMPs적분자식별화작용궤리, 병득도료이자적결합모형.
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.