Eppley Institute for Cancer Research and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198, United States.
J Med Chem. 2011 Jun 23;54(12):4264-8. doi: 10.1021/jm1016413. Epub 2011 May 26.
Carboxy terminal BRCT domains of the breast cancer susceptibility gene 1 (BRCA1) bind to phosphorylated proteins through a pSXXF consensus recognition motif. We report a systematic structure-activity relationship study that maps the BRCT(BRCA1)-pSXXF binding interface, leading to identification of peptides with nanomolar binding affinities comparable to those of the previously reported 13-mer peptides and providing a clear description of the pSXXF-BRCT interface, which is essential for developing small molecule inhibitors via the peptidomimetic approach.
乳腺癌易感基因 1(BRCA1)的羧基末端 BRCT 结构域通过 pSXXF 共有识别基序与磷酸化蛋白结合。我们报告了一项系统的结构-活性关系研究,该研究绘制了 BRCT(BRCA1)-pSXXF 结合界面,鉴定出具有纳摩尔结合亲和力的肽,与先前报道的 13 肽相当,并提供了 pSXXF-BRCT 界面的清晰描述,这对于通过肽模拟方法开发小分子抑制剂至关重要。