Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68022, USA.
J Med Chem. 2012 Apr 12;55(7):3583-7. doi: 10.1021/jm300078z. Epub 2012 Mar 19.
We describe truncation and SAR studies to identify a pentapeptide that binds Cbl tyrosine kinase binding domain with a higher affinity than the parental peptide. The pentapeptide has an alternative binding mode that allows occupancy of a previously uncharacterized groove. A peptide library was used to map the binding site and define the interface landscape. Our results suggest that the pentapeptide is an ideal starting point for the development of inhibitors against Cbl driven diseases.
我们描述了截短和 SAR 研究，以鉴定一种五肽，其与亲本肽相比，与 Cbl 酪氨酸激酶结合域的结合亲和力更高。该五肽具有替代的结合模式，允许占据以前未表征的凹槽。使用肽文库来绘制结合位点并定义界面景观。我们的结果表明，该五肽是开发针对 Cbl 驱动疾病的抑制剂的理想起点。
