2-Bromopalmitate Analogues as Activity-Based Probes To Explore Palmitoyl Acyltransferases

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• 作者：Baohui Zheng ; Michael DeRan ; Xinyan Li ; Xuebin Liao ; Masaki Fukata ; Xu Wu
• 刊名：The Journal of the American Chemical Society
• 出版年：2013
• 出版时间：May 15, 2013
• 年：2013
• 卷：135
• 期：19
• 页码：7082-7085
• 全文大小：297K
• 年卷期：v.135,no.19(May 15, 2013)
• ISSN：1520-5126

文摘

Reversible S-palmitoylation is an important post-translational modification that regulates the trafficking, localization, and activity of proteins. Cysteine-rich Asp-His-His-Cys (DHHC) domain-containing enzymes are evolutionarily conserved protein palmitoyl acyltransferases (PATs). The human genome encodes 23 DHHC-PATs that regulate diverse cellular functions. Although chemical probes and proteomic methods to detect palmitoylated protein substrates have been reported, no probes for direct detection of the activity of PATs are available. Here we report the synthesis and characterization of 2-bromohexadec-15-ynoic acid and 2-bromooctadec-17-ynoic acid, which are analogues of 2-bromopalmitate (2-BP), as activity-based probes for PATs as well as other palmitoylating and 2-BP-binding enzymes. These probes will serve as new chemical tools for activity-based protein profiling to explore PATs, to dissect the functions of PATs in cell signaling and diseases, and to facilitate the identification of their inhibitors.