靶向信号转导和转录激活因子6（STAT6）的Src同源2（SH2）结构域的拟肽抑制剂的合成及体外评价
Synthesis and in Vitro Evaluation of a Peptidomimetic Inhibitor Targeting the Src Homology 2 (SH2) Domain of STAT6.
作者信息
Morlacchi Pietro, Mandal Pijus K, McMurray John S
机构信息
Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center , 1901 East Road, Houston, Texas 77054, United States.
出版信息
ACS Med Chem Lett. 2013 Dec 4;5(1):69-72. doi: 10.1021/ml4003919. eCollection 2014 Jan 9.
Abstract
An improved synthesis of a phosphopeptidomimetic prodrug targeting the Src Homology 2 (SH2) domain of signal transducer and activator of transcription 6 (STAT6) is reported. In our convergent methodology, we employed a phosphotyrosine surrogate active ester harboring pivaloyloxymethyl groups, which efficiently coupled to tert-butylglycinyl proline diarylamide. Biological evaluation of 1 has not been reported. We show that it inhibits STAT6 phosphorylation in intact human bronchial epithelial cells, suggesting potential application in the treatment of asthma.
摘要
报道了一种靶向信号转导和转录激活因子6（STAT6）的Src同源2（SH2）结构域的磷酸肽模拟前药的改进合成方法。在我们的汇聚方法中，我们使用了带有新戊酰氧基甲基的磷酸酪氨酸替代活性酯，其能有效地与叔丁基甘氨酰脯氨酸二芳基酰胺偶联。化合物1的生物学评价尚未见报道。我们表明它能抑制完整人支气管上皮细胞中STAT6的磷酸化，提示其在哮喘治疗中的潜在应用。
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