酵母中青蒿素作用靶点的探索

Exploring artemisinins protein targets in yeast

为了验证前人提出的青蒿素在疟原虫中靶点蛋白的可信性并寻找其直接作用的靶点,用酵母作为模式生物,对候选靶点在酵母中的同源蛋白进行基因改造,研究其对青蒿素抑制作用的影响,并利用与琼脂糖偶联的二氢青蒿素(DHA)寻找与之特异性紧密结合的酵母蛋白。研究发现酵母中的同源蛋白似乎没有在青蒿素抑制中起关健作用;并且未找到能与DHA特异性紧密结合的酵母蛋白。结果表明:过去提出的青蒿素作用靶点可能不正确,并暗示青蒿素可能没有特异专一的蛋白靶点或同时作用于多个靶点。

Previously proposed artemisinin target proteins in malarial parasites were evaluated and new direct artemisinins target proteins were screened using yeast （S. cerevisae） as a model. The yeast genes encoding homologues corresponding to artemisinin target candidates in malarial parasites were modified to test the influence to artemisinin＇ s inhibitory action. Sepharose-eoupled dihydroartemisinin was used to isolate the yeast proteins that may bind strongly to this drug. However, no homologue was found to be mainly responsible for artemisinin＇s inhibitory action and no specific proteins bound potently to dihydroartemisinin. These results, together with previous published data, imply alternative possibilities for the mode of action of artemisinins.