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Structure–Activity Relationship Studies To Probe the Phosphoprotein Binding Site on the Carboxy Terminal Domains of the Breast Cancer Susceptibility Gene 1

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journal contribution
posted on 23.06.2011, 00:00 by Ziyan Yuan, Eric A. Kumar, Smitha Kizhake, Amarnath Natarajan
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.