2. Academic Validation
  3. Design strategy for serine hydroxymethyltransferase probes based on retro-aldol-type reaction

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

  • Nat Commun. 2019 Feb 20;10(1):876. doi: 10.1038/s41467-019-08833-7.
Hiroshi Nonaka 1,  Yuki Nakanishi 2,  Satoshi Kuno 2,  Tomoki Ota 2,  Kentaro Mochidome 2,  Yutaro Saito 2,  Fuminori Sugihara 3,  Yoichi Takakusagi 4 5,  Ichio Aoki 4 5,  Satoru Nagatoishi 6 7,  Kouhei Tsumoto 6 7,  Shinsuke Sando 8 9
Affiliations

Affiliations

  • 1 Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan. hnonaka@chembio.t.u-tokyo.ac.jp.
  • 2 Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
  • 3 Core Instrumentation Facility, Immunology Frontier Research Center and Research Institute for Microbial Diseases, Osaka University, Osaka, 565-0871, Japan.
  • 4 National Institute of Radiological Sciences (NIRS), National Institutes for Quantum and Radiological Science and Technology (QST), Anagawa 4-9-1, Inage, Chiba-city, 263-8555, Japan.
  • 5 Group of Quantum-state Controlled MRI, National Institutes for Quantum and Radiological Science and Technology (QST), Anagawa 4-9-1, Inage, Chiba-city, 263-8555, Japan.
  • 6 Medical Proteomics Laboratory, Institute of Medical Science, The University of Tokyo, 4-6-1, Shiroganedai, Minato-ku, Tokyo, 108-8639, Japan.
  • 7 Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
  • 8 Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan. ssando@chembio.t.u-tokyo.ac.jp.
  • 9 Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan. ssando@chembio.t.u-tokyo.ac.jp.
PMID: 30787298 DOI: 10.1038/s41467-019-08833-7
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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-148545
    SHMT Inhibitor