糖动态修饰与生物识别的原位化学探测  

Chemical tools capable of probing the dynamic glycosylation/deglycosylation processes and sugar-protein interactions in-situ

作　　者：胡习乐 贺晓鹏 Xi-Le Hu;Xiao-Peng He(Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering,Feringa Nobel Prize Scientist Joint Research Center,School of Chemistry and Molecular Engineering,East China University of Science and Technology,Shanghai 200237,China;National Center for Liver Cancer,the International Cooperation Laboratory on Signal Transduction,Eastern Hepatobiliary Surgery Hospital,Shanghai 200438,China)

机构地区：[1]华东理工大学化学与分子工程学院,费林加诺贝尔奖科学家联合研究中心,结构可控先进功能材料及其制备教育部重点实验室,上海200237 [2]中国人民解放军海军军医大学国家肝癌科学中心,“肝癌分子网络调控与靶向干预”教育部重点实验室,上海市肝胆肿瘤生物学重点实验室,上海200438

出　　处：《中国科学：化学》2024年第5期716-725,共10页SCIENTIA SINICA Chimica

基　　金：国家自然科学基金(编号:92253306,82130099,21722801,21572058,21202045);上海市科委国际合作项目(编号:23490711600)资助。

摘　　要：随着人类基因组学与蛋白质组学的蓬勃发展,人类糖组学解码成为了21世纪至关重要的科学命题.然而适用于糖组学研究,尤其是能在活细胞原位精细探测糖生物学信息动态变化的高效、通用化学工具仍相对稀缺.作者团队长期致力于糖动态修饰(生物分子糖基化与去糖基化)和糖介导生物识别(糖与凝集素或其它生物分子选择性相互作用)的原位示踪,发展了多种荧光分子探针原型,实现了上述糖生物学过程的动态探测与免标记高通量筛选.本文将系统介绍上述可用于糖生物学研究的全新化学技术原理,及其在凝集素、病毒、细菌以及哺乳动物细胞等不同结构尺度研究模型上的实用范例,最终提出该类技术方法的后续发展方向.With the rapid advancement of human genomics and proteomics,the study of human glycomics has recently become the focus of many chemists and biologists in the 21st century.Compared to those developed for genomic and proteomic studies,chemical tools for the effective study of the glycomics are much fewer.This account will summarize our recent progress in the development of novel chemical probes for the in-situ detection of the glycosylation/deglycosylation processes of biomolecules and sugar-protein interactions.We will discuss the principles to design fluorescent probes for the super-resolution imaging of sugar-mediated glycobiological processes in cells,and homogeneous fluorogenic arrays for the high-throughput screening of sugar–protein interactions in a label-free manner.A perspective is also given with respect to the future directions of developing chemical tools for the study of glycobiology.

关 键 词：化学生物学 糖组学 荧光探针 动态 原位 活细胞 

分 类 号：Q503[生物学—生物化学]