Palladium-triggered deprotection chemistry for protein activation in living cells

doi:10.1038/NCHEM.1887

	Palladium-triggered deprotection chemistry for protein activation in living cells
	Zhang, Xiaoyu 1; Li, Jie 2; Yu, Juntao 3; Zhao, Jingyi 2; Wang, Jie 3; Zheng, Siqi 2; Lin, Shixian 2; Chen, Long 2; Yang, Maiyun 2; Jia, Shang 2
刊名	NATURE CHEMISTRY
	2014-04-01
卷号	6 期号:4 页码:352-361
ISSN号	1755-4330
DOI	10.1038/NCHEM.1887
文献子类	Article
英文摘要	Employing small molecules or chemical reagents to modulate the function of an intracellular protein, particularly in a gain-of-function fashion, remains a challenge. In contrast to inhibitor-based loss-of-function approaches, methods based on a gain of function enable specific signalling pathways to be activated inside a cell. Here we report a chemical rescue strategy that uses a palladium-mediated deprotection reaction to activate a protein within living cells. We identify biocompatible and efficient palladium catalysts that cleave the propargyl carbamate group of a protected lysine analogue to generate a free lysine. The lysine analogue can be genetically and site-specifically incorporated into a protein, which enables control over the reaction site. This deprotection strategy is shown to work with a range of different cell lines and proteins. We further applied this biocompatible protection group/catalyst pair for caging and subsequent release of a crucial lysine residue in a bacterial Type III effector protein within host cells, which reveals details of its virulence mechanism.
WOS关键词	GENETIC-CODE ; MAMMALIAN-CELLS ; PHOSPHOTHREONINE LYASE ; SMALL MOLECULES ; LYSINE ; SITE ; PHOSPHORYLATION ; CATALYSIS ; PATHWAYS ; TYROSINE
WOS研究方向	Chemistry
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000333396200027
内容类型	期刊论文
源URL	[http://cas-ir.dicp.ac.cn/handle/321008/167344]
专题	大连化学物理研究所_中国科学院大连化学物理研究所
通讯作者	Li, Jie
作者单位	1.Lanzhou Univ, Coll Chem & Chem Engn, Lanzhou 730000, Peoples R China 2.Peking Univ, Key Lab Bioorgan Chem & Mol Engn, Synthet & Funct Biomol Ctr, Beijing Natl Lab Mol Sci,Minist Educ,Coll Chem &, Beijing 100871, Peoples R China 3.Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Xiaoyu,Li, Jie,Yu, Juntao,et al. Palladium-triggered deprotection chemistry for protein activation in living cells[J]. NATURE CHEMISTRY,2014,6(4):352-361.
APA	Zhang, Xiaoyu.,Li, Jie.,Yu, Juntao.,Zhao, Jingyi.,Wang, Jie.,...&Chen, Peng R..(2014).Palladium-triggered deprotection chemistry for protein activation in living cells.NATURE CHEMISTRY,6(4),352-361.
MLA	Zhang, Xiaoyu,et al."Palladium-triggered deprotection chemistry for protein activation in living cells".NATURE CHEMISTRY 6.4(2014):352-361.