Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Sclerotiorin and Isochromophilone IV: Inhibitors of Grb2-Shc Interaction, Isolated from Penicillium multicolor F1753

  • Nam, Ji-Youn (Korea Research Institute of Bioscience and Biotechnology) ;
  • Son, Kwang-Hee (Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim, Hyae-Kyeong (Korea Research Institute of Bioscience and Biotechnology, Department of Biochemistry, Chungbuk National University) ;
  • Han, Mi-Young (Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim, Sung-Uk (Korea Research Institute of Bioscience and Biotechnology) ;
  • Choi, Jung-Do (Department of Biochemistry, Chungbuk National University) ;
  • Kwon, Byoung-Mog (Korea Research Institute of Bioscience and Biotechnology)
  • Published : 2000.08.01
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Abstract

Grb2 is an important adaptor protein in the mitogenic Ras signaling pathway of receptor tyrosine kinases, and contains one SH2 domain and two SH3 domains. The SH2 domain binds to specific phosphotyrosine motifs on receptors or adaptor proteins such as Shc. The SH2 domain antagonists may lead to blocking of the oncogenic Ras signals and to developing new antitumor agents. In the course of screening SH2 antagonists from natural sources, cslerotiorin (1) and isochromophilone IV (2) were isolated from a strain, Penicillium multicolor F1753, and their structures were established by NMR spectral data. The metabolites significantly inhibited the binding between the Grb2-SH2 domain and phosphopeptide derived from the Shc protein, with $IC_{50}$ values of $22{\;}\mu\textrm{M}{\;}and{\;}48{\;}\mu\textrm{M}$ for (1) and (2), respectively. The compounds are the first nonpeptidic inhibitors of the SH2 domain from a natural source.

Keywords

References

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