Inducible gene expression and protein translocation using nontoxic ligands identified by a mammalian three-hybrid screen

Stephen D. Liberles; Steven T. Diver; David J. Austin

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Inducible gene expression and protein translocation using nontoxic ligands identified by a mammalian three-hybrid screen

机译：诱导型基因表达和蛋白易位使用通过哺乳动物三杂交筛选鉴定的无毒配体

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The natural product rapamycin has been used to provide temporal and quantitative control of gene expression in animals through its ability to interact with two proteins simultaneously. A shortcoming of this approach is that rapamycin is an inhibitor of cell proliferation, the result of binding to FKBP12-rapamycin-associated protein (FRAP). To overcome this limitation, nontoxic derivatives of rapamy- cin bearing bulky substituents at its C16-position were syn- thesized, each in a single step. The isosteric isopropoxy and methallyl substituents with the nonnatural C16-configuration abolish both binding to FRAP and inhibition of T cell prolif- eration.

机译：天然产物雷帕霉素已被用来通过其同时与两种蛋白质相互作用的能力提供对动物基因表达的时间和定量控制。该方法的缺点是雷帕霉素是细胞增殖的抑制剂，是与FKBP12-雷帕霉素相关蛋白（FRAP）结合的结果。为了克服这个限制，合成了雷帕霉素在C16位带有大取代基的无毒衍生物，每个衍生物都可以一步完成。具有非天然C16构型的等构异丙氧基和甲基烯丙基取代基消除了与FRAP的结合以及对T细胞增殖的抑制。

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《Proceedings of the National Academy of Sciences of the United States of America》 |1997年第15期|p.7825-7830|共6页
作者
Stephen D. Liberles; Steven T. Diver; David J. Austin;
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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种 eng
中图分类自然科学总论;
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6. Inducible gene expression and protein translocation using nontoxic ligands identified by a mammalian three-hybrid screen [O] . Stephen D. Liberles, Steven T. Diver, David J. Austin, 1997

机译：使用哺乳动物三杂交筛选鉴定的无毒配体诱导基因表达和蛋白质易位
7. Inducible gene expression and protein translocation using nontoxic ligands identified by a mammalian three-hybrid screen [O] . S. D. Liberles, S. T. Diver, D. J. Austin, 1997

机译：使用哺乳动物三杂交筛鉴定的无毒配体的诱导基因表达和蛋白易位
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Inducible gene expression and protein translocation using nontoxic ligands identified by a mammalian three-hybrid screen

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