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

Yusuke Kimura; Toru Komatsu; Kouichi Yanagi; Kenjiro Hanaoka; Tasuku Ueno; Takuya Terai; Hirotatsu Kojima; Takayoshi Okabe; Tetsuo Nagano; Yasuteru Urano

doi:10.1002/anie.201608677

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

Yusuke Kimura, Toru Komatsu, Kouichi Yanagi, Kenjiro Hanaoka, Tasuku Ueno, Takuya Terai, Hirotatsu Kojima, Takayoshi Okabe, Tetsuo Nagano, Yasuteru Urano

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	153-157
Number of pages	5
Journal	Angewandte Chemie - International Edition
Volume	56
Issue number	1
DOIs	https://doi.org/10.1002/anie.201608677
Publication status	Published - 2017 Jan 2
Externally published	Yes

Keywords

activity-based probes
enzymes
fluorogenic probes
inhibitors
methyltransferases

ASJC Scopus subject areas

Catalysis
Chemistry(all)

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10.1002/anie.201608677

Cite this

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abstract = "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.",

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AU - Kimura, Yusuke

AU - Komatsu, Toru

AU - Yanagi, Kouichi

AU - Hanaoka, Kenjiro

AU - Ueno, Tasuku

AU - Terai, Takuya

AU - Kojima, Hirotatsu

AU - Okabe, Takayoshi

AU - Nagano, Tetsuo

AU - Urano, Yasuteru

PY - 2017/1/2

Y1 - 2017/1/2

N2 - 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.

AB - 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.

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KW - enzymes

KW - fluorogenic probes

KW - inhibitors

KW - methyltransferases

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

Abstract

Keywords

ASJC Scopus subject areas

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