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KMID : 0545120000100040544
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Journal of Microbiology and Biotechnology
2000 Volume.10 No. 4 p.544 ~ p.546
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Sclerotiorin and Isochromophilone IV
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NAM, JI-YOUN
SON, KWANG-HEE/KIM, HYAE-KYEONG/HAN, MI-YOUNG/KIM, SUNG-UK/CHOI, JUNG-DO/KWON, BYOUNG-MOG
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Abstract
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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, sclerotiorin (1) and isochromophilone Ⅳ (2) were isolated from a strain, Penicilliwn multicolor F 1753, 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 22μM and 48μM for (1) and (2). respectively. The compounds are the first nonpeptidic inhibitors of the SH2 domain from a natural source.
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KEYWORD
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