Design strategy for serine hydroxymethyltransferase probes based on retro-aldol-type reaction

Hiroshi Nonaka (), Yuki Nakanishi, Satoshi Kuno, Tomoki Ota, Kentaro Mochidome, Yutaro Saito, Fuminori Sugihara, Yoichi Takakusagi, Ichio Aoki, Satoru Nagatoishi, Kouhei Tsumoto and Shinsuke Sando ()
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Hiroshi Nonaka: The University of Tokyo
Yuki Nakanishi: The University of Tokyo
Satoshi Kuno: The University of Tokyo
Tomoki Ota: The University of Tokyo
Kentaro Mochidome: The University of Tokyo
Yutaro Saito: The University of Tokyo
Fuminori Sugihara: Osaka University
Yoichi Takakusagi: National Institutes for Quantum and Radiological Science and Technology (QST)
Ichio Aoki: National Institutes for Quantum and Radiological Science and Technology (QST)
Satoru Nagatoishi: The University of Tokyo, 4-6-1, Shiroganedai, Minato-ku
Kouhei Tsumoto: The University of Tokyo, 4-6-1, Shiroganedai, Minato-ku
Shinsuke Sando: The University of Tokyo

Nature Communications, 2019, vol. 10, issue 1, 1-10

Abstract: Abstract Serine hydroxymethyltransferase (SHMT) is an enzyme that catalyzes the reaction that converts serine to glycine. It plays an important role in one-carbon metabolism. Recently, SHMT has been shown to be associated with various diseases. Therefore, SHMT has attracted attention as a biomarker and drug target. However, the development of molecular probes responsive to SHMT has not yet been realized. This is because SHMT catalyzes an essential yet simple reaction; thus, the substrates that can be accepted into the active site of SHMT are limited. Here, we focus on the SHMT-catalyzed retro-aldol reaction rather than the canonical serine–glycine conversion and succeed in developing fluorescent and 19F NMR molecular probes. Taking advantage of the facile and direct detection of SHMT, the developed fluorescent probe is used in the high-throughput screening for human SHMT inhibitors, and two hit compounds are obtained.

Date: 2019
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08833-7

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DOI: 10.1038/s41467-019-08833-7

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