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.
journal_name
ACS Med Chem Lettjournal_title
ACS medicinal chemistry lettersauthors
Waterson AG,Kennedy JP,Patrone JD,Pelz NF,Feldkamp MD,Frank AO,Vangamudi B,Souza-Fagundes EM,Rossanese OW,Chazin WJ,Fesik SWdoi
10.1021/ml5003629subject
Has Abstractpub_date
2014-11-11 00:00:00pages
140-5issue
2issn
1948-5875journal_volume
6pub_type
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