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Development of Chemical Tools to Monitor and Control Isoaspartyl Peptide Methyltransferase Activity
Author(s) -
Kimura Yusuke,
Komatsu Toru,
Yanagi Kouichi,
Hanaoka Kenjiro,
Ueno Tasuku,
Terai Takuya,
Kojima Hirotatsu,
Okabe Takayoshi,
Nagano Tetsuo,
Urano Yasuteru
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201608677
Subject(s) - chemistry , methyltransferase , peptide , enzyme , biochemistry , combinatorial chemistry , residue (chemistry) , chemical modification , methylation , gene
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.