Year: 2014
Type: article
Abstract: Replication Protein A is the primary eukaryotic ssDNA binding protein that has a central role in initiating the cellular response to DNA damage. RPA recruits multiple proteins to sites of DNA damage via the N-terminal domain of the 70 kDa subunit (RPA70N). Here we describe the optimization of a diphenylpyrazole carboxylic acid series of inhibitors of these RPA-protein interactions. We evaluated substituents on the aromatic rings as well as the type and geometry of the linkers used to combine fragments, ultimately leading to submicromolar inhibitors of RPA70N protein-protein interactions.
Source: ACS Medicinal Chemistry Letters
DOI: 10.1021/ml5003629
Institution: Vanderbilt University
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
Funders: National Science Foundation, U.S. Department of Energy, Cancer Research UK, Deutscher Akademischer Austauschdienst, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Universidade Federal de Minas Gerais, National Institutes of Health, Office of Science, NIH Office of the Director, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Environmental Health Sciences, Argonne National Laboratory
Awards: G102163711, G1054907967, G107546177, G1313983767, G1461844466, G154774999, G1664757510, Console upgrades for biological NMR spectrometers, G2287611682, G2539568006, G262962599, G3075337988, G3233110038, G3485139178, G3601372966, G498139845, Discovery of protein-protein interaction inhibitors of Replication Protein A, G5076956890, G5096900011, G513797252, G5607048534, MRI: Acquisition of a 900 MHz Ultra-High Field NMR Spectrometer, G6848031779, G6918803902, G7097083935, G8708901923, G9000002633, G9000110200, G9000176995, G9000286727, G969889393, G993149817
OpenAlex ID: W2016986415