Investigation of human flap structure-specific endonuclease 1 (FEN1) activity on primer-template models and exploration of a substrate-based FEN1 inhibitor

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• 作者：Sai Ba^a ; Hao Zhang^a ; Jasmine Yiqin Lee^a ; Haixia Wu^a ; Ruijuan Ye^a ; Dejian Huang^b ; Tianhu Li^a ; ^{thli@ntu.edu.sg" class="auth_mail" title="E-mail the corresponding author}
• 关键词：FEN1 ; Phosphorothioate ; Inhibitor ; Primer ; Electrophoresis
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2016
• 出版时间：1 May 2016
• 年：2016
• 卷：24
• 期：9
• 页码：1988-1992
• 全文大小：1220 K

文摘

Flap structure-specific endonuclease 1 (FEN1) is one of the enzymes that involve in Eukaryotic DNA replication and repair. Recent studies have proved that FEN1 is highly over-expressed in various types of cancer cells and is a drug target. However, a limited number of FEN1 inhibitors has been identified and approved. Herein, we investigate the catalytic activity of FEN1, and propose a substrate-based inhibitor. As a consequence, one of the phosphorothioate-modified substrates is proved to exhibit the most efficient inhibitory effect in our in vitro examinations. A novelly-designed substrate-based FEN1 inhibitor was accordingly constructed and determined a remarkable IC₅₀ value.