Investigation of Specific Binding Proteins to Photoaffinity Linkers for Efficient Deconvolution of Target Protein

详细信息    查看全文

• 作者：Jongmin Park ; Minseob Koh ; Ja Young Koo ; Sanghee Lee ; Seung Bum Park
• 刊名：ACS Chemical Biology
• 出版年：2016
• 出版时间：January 15, 2016
• 年：2016
• 卷：11
• 期：1
• 页码：44-52
• 全文大小：604K
• ISSN：1554-8937

文摘

Photoaffinity-based target identification has received recent attention as an efficient research tool for chemical biology and drug discovery. The major obstacle of photoaffinity-based target identification is the nonspecific interaction between target identification probes and nontarget proteins. Consequently, the rational design of photoaffinity linkers has been spotlighted for successful target identification. These nonspecific interactions have been considered as random events, and therefore no systematic investigation has been conducted regarding nonspecific interactions between proteins and photoaffinity linkers. Herein, we report the protein-labeling analysis of photoaffinity linkers containing three photoactivatable moieties: benzophenone, diazirine, and arylazide. Each photoaffinity linker binds to a different set of proteins in a structure-dependent manner, in contrast to the previous conception. The list of proteins labeled by each photoaffinity linker was successfully used to eliminate the nonspecific binding proteins from target candidates, thereby increasing the success rate of target identification.