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Abstract：
Identification of drug targets and biochemical investigations on mechanisms of action are major issues in modern drug development. The present article is a critical review of the classical \"one drug\"-\"one target\" paradigm. In fact, novel methods for target deconvolution and for investigation of resistant strains based on protein mass spectrometry have shown that multiple gene products and adaptation mechanisms are involved in the responses of pathogens to xenobiotics rather than one single gene or gene product. Resistance to drugs may be linked to differential expression of other proteins than those interacting with the drug in protein binding studies and result in complex cell physiological adaptation. Consequently, the unraveling of mechanisms of action needs approaches beyond proteomics. This review is focused on protozoan pathogens. The conclusions can, however, be extended to chemotherapies against other pathogens or cancer.
摘要：
药物靶标的识别和作用机制的生化研究是现代药物开发中的主要问题。本文是对经典的“一种药物”-“一种目标”范式的批判性评论。事实上,基于蛋白质质谱的目标去卷积和抗性菌株研究的新方法表明，多种基因产物和适应机制参与病原体对异源生物的反应，而不是一个单一的基因或基因产物。对药物的抗性可能与其他蛋白质的差异表达有关，而不是在蛋白质结合研究中与药物相互作用的蛋白质，并导致复杂的细胞生理适应。因此,作用机制的解开需要蛋白质组学以外的方法。本文主要对原生动物病原体进行综述。结论可以,然而,扩展到针对其他病原体或癌症的化学疗法。
