Development of Chemical Tools to Monitor and Control Isoaspartyl Peptide Methyltransferase Activity

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• 作者：Yusuke Kimura ; Dr. Toru Komatsu ; Kouichi Yanagi ; Dr. Kenjiro Hanaoka ; Dr. Tasuku Ueno ; Dr. Takuya Terai ; Prof. Dr. Hirotatsu Kojima ; Prof. Dr. Takayoshi Okabe ; Prof. Dr. Tetsuo Nagano and Prof. Dr. Yasuteru Urano
• 刊名：Angewandte Chemie
• 出版年：2017
• 出版时间：January 2, 2017
• 年：2017
• 卷：129
• 期：1
• 页码：159-163
• 全文大小：2913K
• ISSN：1521-3757

文摘

We have established a coupled assay system targeting protein l-isoaspartyl methyltransferase (PIMT), a key enzyme in the metabolism of isoaspartyl peptides and proteins. The system utilizes a fluorogenic peptide probe containing an isoaspartyl residue at the P1′ position of the caspase-3 recognition sequence. Following PIMT-catalyzed methyl transfer reaction, the methylated probe is specifically cleaved by caspase-3 to give fluorescence activation. High-throughput screening of our chemical library with this assay system identified PIMT inhibitors that may be useful as leads in the design of chemical probes for controlling PIMT activity.