Diphenylpyrazoles as Replication Protein A Inhibitors
2014; American Chemical Society; Volume: 6; Issue: 2 Linguagem: Inglês
10.1021/ml5003629
ISSN1948-5875
AutoresAlex G. Waterson, J. Phillip Kennedy, James D. Patrone, Nicholas F. Pelz, Michael D. Feldkamp, Andreas O. Frank, Bhavatarini Vangamudi, Elaine M. Souza–Fagundes, Olivia W. Rossanese, Walter Chazin, Stephen W. Fesik,
Tópico(s)Bacterial Genetics and Biotechnology
ResumoReplication 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.
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