Diphenylpyrazoles as Replication Protein A inhibitors [electronic resource]

• Ngôn ngữ: eng
• Ký hiệu phân loại: 612 Human physiology
• Thông tin xuất bản: Washington, D.C. : Oak Ridge, Tenn. : United States. Dept. of Energy. Office of Science ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2014
• Mô tả vật lý: Size: p. 140-145 : , digital, PDF file.
• Bộ sưu tập: Metadata
• ID: 261374
• Chủ đề: 1. 37 inorganic, organic, physical, and analytical chemistry; 2. 60 applied life sciences; 3. Fragment-based discovery; 4. Medicinal chemistry; 5. Replication protein a

Tóm tắt

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. Lastly, 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.