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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.

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.

SUBMITTER: Yuan Z

PROVIDER: S-EPMC3117075 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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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.

Yuan Ziyan Z Kumar Eric A EA Kizhake Smitha S Natarajan Amarnath A

Journal of medicinal chemistry 20110526 12

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 developin ...[more]

PMID: 21574625

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