title: Investigation of human flap structure-specific endonuclease 1 (FEN1) activity on primer-template models and exploration of a substrate-based FEN1 inhibitor.
abstract: 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.
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore 637371, Singapore.
authors.forename: Sai
authors.initials: S
authors.lastname: Ba
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore 637371, Singapore.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore 637371, Singapore.
authors.forename: Jasmine Yiqin
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore 637371, Singapore.
authors.forename: Haixia
authors.initials: H
authors.lastname: Wu
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore 637371, Singapore.
authors.forename: Ruijuan
authors.initials: R
authors.lastname: Ye
authors.affiliation: Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore.
authors.forename: Dejian
authors.initials: D
authors.lastname: Huang
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore 637371, Singapore. Electronic address: thli@ntu.edu.sg.
authors.forename: Tianhu
authors.initials: T
authors.lastname: Li
mesh_terms: D045585:Flap Endonucleases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D013379:Substrate Specificity
chemical_list: D045585:Flap Endonucleases; C468317:FEN1 protein, human
keywords: Electrophoresis; FEN1; Inhibitor; Phosphorothioate; Primer