清华大学医学与生命科学院的周玉祥教授介绍,他们在使用DNA芯片进行药物研究过程中,揭示了土槿皮酸B抑制真菌的新机制。
与传统方法相比,生物芯片具有快速、准确的优势,它可以在经药物处理的细胞与未处理的细胞之间一次性比较千万个基因表达,找出两者之间的差异变化,从而推断出药物作用机制,评价其活性与毒性,进而寻找药物作用靶点或找到新的药物。
试验显示,土槿皮酸B处理酵母菌细胞90分钟后,其生长率大大下降。研究人员对两万多个基因进行了比较后发现,酵母菌细胞的CTS1基因和EGT2基因分别被抑制了5.4和3.8倍,从而减少了几丁质酶和内切葡聚糖酶的合成,而两者都是子细胞从母细胞脱落的必需酶,也就是说土槿皮酸B阻碍了真菌的分裂繁殖过程。据悉,土槿皮酸B的这种抗真菌机制和当前众多抗真菌的机制不同,有望发展成为一种新的抗真菌药物。
周玉祥个人主页
http://www.biosci.tsinghua.edu.cn:8001/faculty/zhouyx.html
代表性论文:
Zhang L, Zhang Y, Zhou Y. M., An, S., Zhou Y. X., Cheng, J., Expression profiling of the response of saccharomyces cerevisiae to 5-fluorocytosine using a DNA microarray, International Journal of Antimicrobial Agents, (2002)
Sun, B., Xie, W., Yi, G., Chen, D. and Zhou, Y., Cheng, J. (2001).
“Microminiaturized immunoassays using quantum dots as fluorescent label by laser confocal scanning fluorescence detection”, Journal of Immunological Methods, 249: 85-89.
张亮、张坚、周玉祥、程京, DNA 芯片技术中利用内标对数据归一化后检测基因的表达变化,中国生物化学与分子生物学学报 (2002), Vol.18, No.1, 115-119
张亮、张岩、周玉祥、程京, 用聚类法分析受抗真菌物质处理后的酵母全基因表达谱, 生物化学与生物物理进展, (2002)
Electron paramagnetic resonance and oxygen binding studies of α-nitrosyl hemoglobin-a novel oxygen carrier having NO- assisted allosteroc functions, J Biol Chem, 1998, Vol.273, No.32: 20323~20333.
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