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.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Moeller BJ,Sidman RL,Pasqualini R,Arap Wdoi
10.1158/0008-5472.CAN-10-2361subject
Has Abstractpub_date
2011-03-01 00:00:00pages
1816-24issue
5eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-10-2361journal_volume
71pub_type
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