类乳腺癌易感基因BRCA1肽的设计、合成及与抑癌基因蛋白RAD51肽段的相互作用  

Design and Synthesis of Breast Cancer Susceptibility Gene BRCA1 Analogs Peptides and the Interaction of Analogs Peptides with Breast Cancer Suppressor Gene Protein RAD51

作　　者：李林璐 吕名秀[1,2] 卢奎 刘广斌 彭露[2] 

机构地区：[1]郑州大学化学与分子工程学院,郑州450001 [2]河南工程学院材料与化学工程学院,郑州450007 [3]郑州工程技术学院化工食品学院,郑州450044

出　　处：《有机化学》2018年第1期246-252,共7页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(Nos.21572046;21172054)资助项目~~

摘　　要：乳腺癌易感基因BRCA1肽对抑制女性乳腺癌病发有积极作用,其与乳腺癌细胞内抑癌基因蛋白RAD51相互作用的研究是乳腺癌药物发现的重要部分.通过Discovery Studio模拟类BRCA1肽与RAD51对接过程,利用R-DOCK评价系统从结果中筛选出4条评分较高的类BRCA1肽,采用固相逐步合成法制得.通过荧光光谱、圆二色光谱等方法研究了其与RAD51肽段(Pep158-180、Pep181-200、Pep241-260)的相互作用,发现4条类BRCA1肽的作用都强于BRCA1肽,这与模拟的结果相一致,其中BRCA1-3与RAD51的两个关键肽段(Pep158-180、Pep241-260)的相互作用明显强于BRCA1肽和其他类肽.该研究结果为乳腺癌药物分子设计提供了依据.Peptide breast cancer susceptibility gene BRCA1 plays an active role in inhibiting female breast cancer. The interaction between BRCA1 and breast cancer suppressor gene protein RAD51 in cancer cell is also an essential part for the treatment of breast cancer. Discovery Studio simulation of the docking process of BRCA1 analogs and RAD51 was used to screen the BRCA1 analogs with different charge and acid-base properties. The R-DOCK evaluation system is used to screened out 4 higher BRCA1 like peptides from the results, and the interactions with BRCA1 analogs of RAD51 peptides（Pep158-180, Pep181-200 and Pep241-260） were studied by using fluorescence spectroscopy and CD spectroscopy. The results indicate that acid-base properties of BRCA1 analogs have great influence on their interaction. The results showed that the effect of BRCA1-3 to RAD51（Pep158-180/Pep241-260） which is the two key peptides were obviously higher than the other parent peptide. Besides, compared with BRCA1, all BRCA1 analogs combined with RAD51 much closer. The results provide evidence to design novel breast drugs for breast cancer.

关 键 词：类BRCA1肽 RAD51肽段 荧光光谱 圆二色光谱 DS模拟 

分 类 号：TQ460.1[化学工程—制药化工]