化学基元组学与药物创新  

Chemomics and drug innovation

作　　者：徐峻[1] 顾琼[1] 刘海波[2] 周家驹[1] 卜宪章[1] 黄志纾[1] 鲁桂[1] 李丁[1] 魏冬青[3] 王领[1] 古练权[1] 

机构地区：[1]中山大学药学院药物分子设计研究中心,中山大学人类病毒学研究所,广州510006 [2]中国医学科学院药用植物研究所,北京100194 [3]上海交通大学药学生命科学技术学院生物信息生物统计系,上海200240

出　　处：《中国科学：化学》2013年第1期18-34,共17页SCIENTIA SINICA Chimica

基　　金：科技部药物创新重大专项(2010ZX09102-305);广东省创新人才团队引进专项(2009010058);国家高技术研究发展计划(863计划;2012AA020307);国家自然科学基金(81173470)资助

摘　　要：化学基元组学(chemomics)是与化学信息学、生物信息学、合成化学等学科相关的交叉学科.生物系统从内源性小分子(天然砌块)出发,通过酶催化的化学反应序列制造天然产物.生物系统通过化学反应和天然砌块向目标天然产物"砌入"一组原子,这样的一组原子称为化学基元(chemoyl).化学基元组(chemome)是生物组织中所含有的化学基元的全体.化学基元组学研究各种化学基元的结构、组装与演化的基本规律.在生存压力和繁衍需求的驱动下,生物系统已经进化出有效手段来合成天然产物以应付环境的变化,并产生了丰富多彩的生物和化学多样性.近年来,人们意识到药物创新的瓶颈之一是药物筛选资源的日益枯竭.化学基元组学可以解决这个瓶颈问题,它通过揭示生物系统制备化学多样性的规律,发展仿生合成方法制备类天然化合物库(quasi natural product libraries)以供药物筛选.本文综述了化学基元组学的主要研究内容及其在药物创新各领域中的潜在应用.Chemomics is an interdisciplinary study using approaches from chemoinformatics, bioinformatics, synthetic chemistry, and other related disciplines. Biological systems make natural products from endogenous small molecules （natural product building blocks） through a sequence of enzyme catalytic reactions. For each reaction, the natural product building blocks may contribute a group of atoms to the target natural product. We describe this group of atoms as a chemoyl. A chemome is the complete set of chemoyls in an organism. Chemomics studies chemomes and the principles of natural product syntheses and evolutions. Driven by survival and reproductive demands, biological systems have developed effective protocols to synthesize natural products in order to respond to environmental changes; this results in biological and chemical diversity. In recent years, it has been realized that one of the bottlenecks in drug discovery is the lack of chemical resources for drug screening. Chemomics may solve this problem by revealing the rules governing the creation of chemical diversity in biological systems, and by developing biomimetic synthesis approaches to make quasi natural product libraries for drug screening. This treatise introduces chemomics and outlines its contents and potential applications in the fields of drug innovation.

关 键 词：化学基元组 化学信息学 生物信息学 药物创新 仿生合成 

分 类 号：R914[医药卫生—药物化学]