研究乳腺癌易感基因 1 的羧基末端结构域上的磷酸蛋白结合位点的构效关系。
Structure-activity relationship studies to probe the phosphoprotein binding site on the carboxy terminal domains of the breast cancer susceptibility gene 1.
机构信息
Eppley Institute for Cancer Research and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198, United States.
出版信息
J Med Chem. 2011 Jun 23;54(12):4264-8. doi: 10.1021/jm1016413. Epub 2011 May 26.
Abstract
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.
摘要
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。
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