alexa Discovery of DNA repair inhibitors by combinatorial library profiling.
Oncology

Oncology

Journal of Cancer Science & Therapy

Author(s): Moeller BJ, Sidman RL, Pasqualini R, Arap W

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Abstract Small molecule inhibitors of DNA repair are emerging as potent and selective anticancer therapies, but the sheer magnitude of the protein networks involved in DNA repair processes poses obstacles to discovery of effective candidate drugs. To address this challenge, we used a subtractive combinatorial selection approach to identify a panel of peptide ligands that bind DNA repair complexes. Supporting the concept that these ligands have therapeutic potential, we show that one selected peptide specifically binds and noncompetitively inactivates DNA-PKcs, a protein kinase critical in double-strand DNA break repair. In doing so, this ligand sensitizes BRCA-deficient tumor cells to genotoxic therapy. Our findings establish a platform for large-scale parallel screening for ligand-directed DNA repair inhibitors, with immediate applicability to cancer therapy. ©2011 AACR.
This article was published in Cancer Res and referenced in Journal of Cancer Science & Therapy

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