目的 探讨从化合物库中高通量筛选得到的、可有效抑制结核分枝杆菌生长和繁殖的新型活性化合物S28 的作用机制及其可能的作用靶点。方法 采用双向电泳技术, 比较分析活性化合物作用于结核分枝杆菌H37Ra 前、后的全细胞蛋白表达差异。结果 13 个蛋白质斑点表达下调, 对其中6 个改变明显的蛋白质斑点进行基质辅助激光解吸/ 电离飞行时间质谱分析, 成功测定2 个蛋白质斑点。数据库检索分析确定这2 个差异蛋白点分别为延长因子Tu 和短链脱氢酶, 是参与蛋白质翻译和氧化呼吸、能量代谢等生理过程的重要蛋白。结论 为 进一步深入探索新型抗结核活性化合物的作用机制和可能的靶点提供研究基础和方向。

Objective To explore the mechanismand possible drug target of the new anti-tuberculosis compound, S28, which is effective on Mycobacterium tuberculosis in vitro.Methods Two dimensional gel electrophoresis ( 2 - DE) was employed to determine the effects of this compound on the expression of Mycobacterium tuberculosis proteome. Global proteome of Mycobacterium tuberculosis strain H37Ra was treated with S28 and compared with control ( untreated) . Results The expression of 13 proteins was decreased; six
proteins, which were remarkably decreased in Mycobacterium tuberculosis treated with S28, were subjected to matrix assisted laser adsorption/ionization time-of-flight mass spectrometry ( MALDI - TOF- MS) analysis and the nature of two proteins was successfully determined. They were identified as elongation factor Tu and short chain dehydrogenase, which play important roles in protein translation and energy metabolism. Conclusion These data provide insight into potential novel anti-tuberculosis mechanisms and drug targets.