2. Academic Validation
  3. Establishment of an MR1 Presentation Reporter Screening System and Identification of Phenylpropanoid Derivatives as MR1 Ligands

Establishment of an MR1 Presentation Reporter Screening System and Identification of Phenylpropanoid Derivatives as MR1 Ligands

  • J Med Chem. 2023 Sep 14;66(17):12520-12535. doi: 10.1021/acs.jmedchem.3c01122.
Takuro Matsuoka 1,  Akira Hattori 1,  Shinya Oishi 1,  Mitsugu Araki 2,  Biao Ma 3,  Toshiki Fujii 1,  Norihito Arichi 1,  Yasushi Okuno 2 3,  Hideaki Kakeya 1,  Sho Yamasaki 4 5,  Hiroaki Ohno 1,  Shinsuke Inuki 1
Affiliations

Affiliations

  • 1 Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
  • 2 Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
  • 3 RIKEN Center for Computational Science, Chuo-ku, Kobe 650-0047, Japan.
  • 4 Research Institute for Microbial Diseases, Osaka University, Suita 565-0871, Japan.
  • 5 Immunology Frontier Research Center (IFReC), Osaka University, Suita 565-0871, Japan.
PMID: 37638616 DOI: 10.1021/acs.jmedchem.3c01122
Abstract

Mucosal-associated invariant T (MAIT) cells are innate-like T cells that are modulated by ligands presented on MHC class I-related proteins (MR1). These cells have attracted attention as potential drug targets because of their involvement in the initial response to Infection and various disorders. Herein, we have established the MR1 presentation reporter assay system employing split-luciferase, which enables the efficient exploration of MR1 ligands. Using our screening system, we identified phenylpropanoid derivatives as MR1 ligands, including coniferyl aldehyde, which have an ability to inhibit the MR1-MAIT cell axis. Further, the structure-activity relationship study of coniferyl aldehyde analogs revealed the key structural features of ligands required for MR1 recognition. These results will contribute to identifying a broad range of endogenous and exogenous MR1 ligands and to developing novel MAIT cell modulators.

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