清華大學(xué)醫(yī)學(xué)與生命科學(xué)院的周玉祥教授介紹,,他們?cè)谑褂肈NA芯片進(jìn)行藥物研究過(guò)程中,,揭示了土槿皮酸B抑制真菌的新機(jī)制。
與傳統(tǒng)方法相比,,生物芯片具有快速,、準(zhǔn)確的優(yōu)勢(shì),它可以在經(jīng)藥物處理的細(xì)胞與未處理的細(xì)胞之間一次性比較千萬(wàn)個(gè)基因表達(dá),,找出兩者之間的差異變化,,從而推斷出藥物作用機(jī)制,評(píng)價(jià)其活性與毒性,,進(jìn)而尋找藥物作用靶點(diǎn)或找到新的藥物,。
試驗(yàn)顯示,土槿皮酸B處理酵母菌細(xì)胞90分鐘后,,其生長(zhǎng)率大大下降,。研究人員對(duì)兩萬(wàn)多個(gè)基因進(jìn)行了比較后發(fā)現(xiàn),,酵母菌細(xì)胞的CTS1基因和EGT2基因分別被抑制了5.4和3.8倍,從而減少了幾丁質(zhì)酶和內(nèi)切葡聚糖酶的合成,,而兩者都是子細(xì)胞從母細(xì)胞脫落的必需酶,,也就是說(shuō)土槿皮酸B阻礙了真菌的分裂繁殖過(guò)程,。據(jù)悉,土槿皮酸B的這種抗真菌機(jī)制和當(dāng)前眾多抗真菌的機(jī)制不同,,有望發(fā)展成為一種新的抗真菌藥物,。
周玉祥個(gè)人主頁(yè)
http://www.biosci.tsinghua.edu.cn:8001/faculty/zhouyx.html
代表性論文:
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.
張亮,、張堅(jiān),、周玉祥,、程京, DNA 芯片技術(shù)中利用內(nèi)標(biāo)對(duì)數(shù)據(jù)歸一化后檢測(cè)基因的表達(dá)變化,,中國(guó)生物化學(xué)與分子生物學(xué)學(xué)報(bào) (2002),, Vol.18, No.1, 115-119
張亮,、張巖、周玉祥,、程京, 用聚類法分析受抗真菌物質(zhì)處理后的酵母全基因表達(dá)譜, 生物化學(xué)與生物物理進(jìn)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.
The Correlation Between Interactions with Oxygen and Allosteric Effects and the Quaternary Structure Oxygen affinity of a-nitrosyl Hemoglobins Biophys. J., Vol 72, No.2, part 2, 1997
Study of the UV Difference Spectra and Electrophoresis of Recombination of Lanthanides and Calmodulin. Science Bulletin(China), Vol.41, No.22, 1905-1911, 1996.
1H NMR and Spin-Labeled EPR Studies on the Interaction of Calmodulin with Jujuboside A Biochem. Biophys. Research Communication, 1994, Vol. 202, No. 1, 148-154.
Sequential Changes of the Fe-Histidine Bond upon ligand Binding to Hemoglobin: Resonance Raman Study of a-aCross-linkedCo-Fe hybrid Hbs. J. Amer. Chem. Soc. (1994), 116: 1683-1689.
Oxygen Equilibrium Studies of Crosslinked Iron-Cobalt Hybrid Hbs: Models for Partially Ligated Intermediates of Cobalt-hemoglobins. J. Biol. Chem. (1993), Vol. 268, No. 31: 23033-23040.