Sturgeon Christopher M, Kemmer Danielle, Anderson Hilary J, Roberge Michel
Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.
Biotechnol J. 2006 Mar;1(3):289-98. doi: 10.1002/biot.200500039.
Knowledge of the spectrum of cellular proteins targeted by experimental therapeutic agents would greatly facilitate drug development. However, identifying the targets of drugs is a daunting challenge. The yeast Saccharomyces cerevisiae is a valuable model organism for human diseases and pathways because it is genetically tractable and shares many functional homolog with humans. In yeast, it is possible to increase or decrease the expression level of essentially every gene and measure changes in drug sensitivity to uncover potential targets. It is also possible to infer mechanism of action from comparing the changes in mRNA expression elicited by drug treatment with those induced by gene deletions or by other drugs. Proteins that bind drugs directly can be identified using yeast protein chips. This review of the use of yeast for discovering targets of drugs discusses the advantages and drawbacks of each approach and how combining methods may reveal targets more efficiently.
了解实验治疗药物所靶向的细胞蛋白质谱将极大地促进药物开发。然而，确定药物的靶点是一项艰巨的挑战。酿酒酵母是研究人类疾病和通路的一种有价值的模式生物，因为它在遗传上易于操作，并且与人类有许多功能同源物。在酵母中，可以增加或降低几乎每个基因的表达水平，并测量药物敏感性的变化以发现潜在靶点。通过比较药物处理引起的mRNA表达变化与基因缺失或其他药物诱导的变化，也有可能推断作用机制。可以使用酵母蛋白质芯片鉴定直接与药物结合的蛋白质。这篇关于利用酵母发现药物靶点的综述讨论了每种方法的优缺点，以及如何结合多种方法可能更有效地揭示靶点。
