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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Discovery of Protein-Protein Interaction Inhibitors of Replication Protein A.

Authors: Patrone, James D; Kennedy, J Phillip; Frank, Andreas O; Feldkamp, Michael D; Vangamudi, Bhavatarini; Pelz, Nicholas F; Rossanese, Olivia W; Waterson, Alex G; Chazin, Walter J; Fesik, Stephen W

Published In ACS Med Chem Lett, (2013 Jul 11)

Abstract: Replication Protein A (RPA) is a ssDNA binding protein that is essential for DNA replication and repair. The initiation of the DNA damage response by RPA is mediated by protein-protein interactions involving the N-terminal domain of the 70 kDa subunit with partner proteins. Inhibition of these interactions increases sensitivity towards DNA damage and replication stress and may therefore be a potential strategy for cancer drug discovery. Towards this end, we have discovered two lead series of compounds, derived from hits obtained from a fragment-based screen, that bind to RPA70N with low micromolar affinity and inhibit the binding of an ATRIP-derived peptide to RPA. These compounds may offer a promising starting point for the discovery of clinically useful RPA inhibitors.

PubMed ID: 23914285 Exiting the NIEHS site

MeSH Terms: No MeSH terms associated with this publication

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