靶向金属酶的金属结合药效特征研究进展

李根; 宁香丽; 李国菠

靶向金属酶的金属结合药效特征研究进展

四川大学华西药学院药物化学系, 四川成都 610041

基金项目:

国家自然科学基金资助项目（No：81874291）；四川省国际合作项目（No：2018HH0100）

详细信息

作者简介:
李根: 李国菠:2014年博士毕业于四川大学药物化学专业,2014-2016年先后在四川大学和牛津大学从事博士后研究。2016年10月加入四川大学华西药学院工作,现任药物化学系副教授,硕士生导师、博士生导师,主要从事药物设计、药物化学及化学生物学等研究,在药物设计新方法、靶向金属酶的创新药物发现等方向取得了重要研究进展。主持了国家自然科学基金面上项目、青年项目、四川省国际合作项目等多项科研项目,以第一或通讯作者在J Med Chem、Chem Sci、Med Res Rev、Bioinformatics、J Chem Inf Model、Eur J Med Chem等期刊发表SCI论文30余篇,已获授权国家发明专利3项,获授权计算机软件著作权5项。曾获教育部自然科学一等奖、四川省科技进步奖一等奖等。

通讯作者:
李国菠, 博士生导师

中图分类号: R914.2
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出版历程
- 收稿日期: 2020-07-09

Recent Advances in Metal Binding Pharmacophores Targeting Metalloenzymes

Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China

More Information

Corresponding author:
Li Guobo, 博士生导师

摘要

摘要: 金属酶广泛存在于各种生物体，与人类疾病发生发展密切相关，是一大类重要的药物作用靶标。尽管已有若干靶向金属酶抑制剂批准用于临床，但大多数金属酶还缺乏特异性药物分子或尚未开发，靶向金属酶的创新药物研究仍然是目前重要领域之一。鉴于金属酶活性位点含金属离子的特殊性，金属酶抑制剂通常包含与活性位点金属离子形成配位的金属结合药效特征（MBP）。通过对挖掘的MBP数据进行归类总结，列举部分经典与少见的MBP类型，并分析对金属酶的选择性和杂泛性，期望能为靶向金属酶的创新药物研究提供线索和借鉴。
- 金属酶 /
- 金属结合药效特征 /
- 杂泛性 /
- 金属酶选择性 /
- 金属酶药物关联信息
Abstract: Metalloenzymes are widely distributed in a variety of organisms, and closely related with human diseases, which hence are considered as a wide range of important drug targets. Although several inhibitors targeting metalloenzymes have been approved for clinical use, there are a lack of drug candidates or high-quality inhibitors for most metalloenzymes, of which even many have not been exploited. Discovery of novel drugs targeting metalloenzymes is still one of important fields. Due to the distinctiveness of metal ions-containing active sites of metalloenzymes, the metalloenzyme inhibitors often bear a specific chemical moiety that is positioned to coordinate with active site metal ions, which is termed metal-binding pharmacophore (MBP). This review summarized the MBP data extracted from metalloenzyme-ligand interaction analyses, enumerated some classic MBPs, and analyzed the metalloenzyme selectivity and promiscuity. These information will provide clues and references for future innovative drug discovery targeting metalloenzymes.
- metalloenzyme /
- metal binding pharmacophore /
- promiscuity /
- metalloenzyme selectivity /
- metalloenzyme-ligand association

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期刊类型引用(2)

1.	高璐，褚志文，李国菠. 基于药物化学课程内容的新药研发前沿案例构建——循环系统药物章节案例教学举例. 大学化学. 2023(12): 25-31 . 百度学术
2.	余俊霖，李国菠. 计算机辅助金属酶靶向药物发现的研究进展. 中国现代应用药学. 2022(21): 2828-2833 . 百度学术