CD47细胞膜亲和色谱在线液相色谱质谱联用系统的建立及其在温郁金抗肝癌活性成分筛选中的应用

批准号:
81503219
项目类别:
青年科学基金项目
资助金额:
18.0 万元
负责人:
楚楚
依托单位:
学科分类:
H3203.中药药效物质
结题年份:
2018
批准年份:
2015
项目状态:
已结题
项目参与者:
颜继忠、李庆勇、陈岑、李清、王小平、熊晴
国基评审专家1V1指导 中标率高出同行96.8%
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中文摘要
恶性肿瘤是世界严重的公共卫生问题,积极开发防治恶性肿瘤的新型药物是当今肿瘤研究的重点和热点。CD47是一个针对性干扰CD47-SIRPa相互作用的靶标,CD47抑制剂的筛选已成为抗肿瘤药物研究的热点课题。从天然产物中寻找CD47抑制剂,对提高癌症化疗疗效,解释中药的增效减毒效应十分重要。本项目拟以CD47受体为靶标,立足前期研究的一种新型细胞膜亲和色谱柱,构建羟乙基磷酰胆碱细胞膜亲和色谱在线液相色谱-质谱联用系统,以结构多样、活性良好的传统中药温郁金为对象,利用细胞膜色谱在线液质联用、高速逆流色谱、中压柱色谱等技术对CD47结合成分进行初步筛选、分离、鉴定,同时还将对筛选到的结合成分进行抗肿瘤活性验证,从温郁金中为肝癌的有效治疗挖掘一些靶向、高效和低毒的药物。同时,该技术平台的建立,也将为细胞膜亲和色谱技术的转化研究提供一个有力范例,为中药药效物质基础的研究提供一条新的思路。
英文摘要
Malignant tumor is a serious public health problem all over the world. One of the most important and hottest spots in the field of tumor research is exploration of new drug with anti-tumor effect. CD47 is a drone which has been reported to possess the activity in interfering in the interaction of CD47-SIRPa. Therefore, screening inhibitor of CD47 becomes to be a hot topic in the development of anti-tumor drug. Natural products resource is a large treasure for exploration of CD47 inhibitor. The inhibitors from natural products may increase the effect of chemo-treatment. And it will be very significant in explanation on the theory of synergy and atenuation of Traditional Chinese Medicines (TCMs) when combined with chemical medicines against tumor. Based on a novel cell membrane chromatographic column acting on CD47 studied in our preliminary research, a 2-methacryloyloxyethyl phosphorylcholine (MPC) cell membrane affinity chromatography (CMAC) online-high performance liquid chromatography/mass spectrometry (HPLC/MS) method will be developed in this study for screening CD47 binding components from TCMs. A traditional herbal medicine of Curcuma wenyujin with exact anti-tumor effect wil be used as an example for validation the method and screening the CD47 binding components which may against liver cancer. Many techniques such as CMAC online HPLC/MS system, high speed counter current chromatography and medium pressure liquid chromatography will be used in screening, isolation and purification of CD47 binding components. Finally, the obtained components will be test and verified for their anti-tumor activity. Our research aims to excavate some anti-cancer drugs with high targeting, effective and low toxicity from TCMs. Moreover, the development of this platform will provide a powerful model in transformation of theory to application of cell membrane chromatography, and offer a new pathway for the pharmacodynamic material basis study of TCMs.
CD47是细胞表面一个重要的"self"标记,是一个针对性干扰CD47-SIRPa相互作用的靶标,其抑制剂的筛选已成为抗肿瘤药物研究的热点课题。从巨大的天然产物库中寻找CD47抑制剂,前景广阔。本项目以CD47受体为靶标,通过对聚合溶液中致孔剂与单体组成、功能单体与交联剂组成、致孔剂组成比例、细胞破碎度、细胞用量等参数的优化,创新性地建立了一种新型细胞膜亲和色谱柱,通过对构建羟乙基磷酰胆碱细胞膜亲和色谱在线液相色谱平台对温郁金中的CD47结合成分进行筛选,筛选到两个结合成分,并进行抗肿瘤活性验证。同时,我们建立了新型的微提取-含量测定方法对温郁金类药材进行质量分析,并基于络合反应研究了一种以高速逆流色谱快速有效分离β-榄香烯的工艺。该研究有效地从温郁金中为肝癌的治疗挖掘到了一些靶向、高效和低毒的小分子成分。此外,该技术平台的建立,也为细胞膜亲和色谱技术的转化研究提供一个有力范例,为中药药效物质基础的研究提供一条新的思路。在本课题的资助下,共发表SCI研究论文7篇,申请国家发明专利3项,培养硕士生5名。
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
Quantitative analysis of sesquiterpenes and comparison of three Curcuma wenyujin herbal medicines by micro matrix solid phase dispersion coupled with MEEKC
微基质固相分散联合MEEKC对倍半萜类化合物的定量分析及三种温郁金药材的比较
DOI:10.1002/elps.201700454
发表时间:2018-02
期刊:Electrophoresis
影响因子:2.9
作者:楚楚
通讯作者:楚楚
DOI:https://doi.org/10.1016/j.aca.2018.08.027
发表时间:2018
期刊:Analytica Chimica Acta
影响因子:6.2
作者:楚楚;魏蒙蒙
通讯作者:魏蒙蒙
Over 1000-fold improvement in an online preconcentration of trace anionic compounds by capillary electrophoresis with ionic liquid micelle-based three-step stacking
使用基于离子液体胶束的三步堆积毛细管电泳将痕量阴离子化合物的在线预浓缩提高了 1000 倍以上
DOI:10.1016/j.aca.2018.08.027
发表时间:2018
期刊:Analytica Chimica Acta
影响因子:6.2
作者:楚楚;魏蒙蒙
通讯作者:魏蒙蒙
Micro-matrix solid-phase dispersion coupled with MEEKC for quantitative analysis of lignans in Schisandrae Chinensis Fructus using molecular sieve TS-1 as a sorbent
微基质固相分散体耦合MEEKC以TS-1分子筛为吸附剂定量分析五味子中的木脂素
DOI:10.1016/j.jchromb.2017.08.024
发表时间:2017-09-15
期刊:JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
影响因子:3
作者:Chu, Chu;Wei, Mengmeng;Yan, Jizhong
通讯作者:Yan, Jizhong
Molecular-sieve-based matrix solid-phase extraction cojourmbined with field-amplified sample stacking in capillary electrophoresis for the determination of three organic acids in a complex solid matrix
基于分子筛的基质固相萃取与毛细管电泳中的场放大样品堆积相结合,用于测定复杂固体基质中的三种有机酸
DOI:--
发表时间:2018
期刊:Journal of Separation Science
影响因子:3.1
作者:楚楚
通讯作者:楚楚
新型金属有机框架固定化酶多级筛选策略的
构建及在高效发掘白及酪氨酸酶抑制剂中的
应用
- 批准号:Y24H280076
- 项目类别:省市级项目
- 资助金额:0.0万元
- 批准年份:2024
- 负责人:楚楚
- 依托单位:
基于多模态辨识和"肠道菌群-胆汁酸"代谢轴探究乌药防治高脂血症的药效物质基础和作用机制
- 批准号:82374017
- 项目类别:面上项目
- 资助金额:48万元
- 批准年份:2023
- 负责人:楚楚
- 依托单位:
国内基金
海外基金
