The first small fluorescent probe as Tyrosyl-DNA phosphodiesterase 1 (TDP1) substrate. (October 2019)

• Record Type: Journal Article
• Authors: Tang, Zhan-Yong; Zhang, Yu; Chen, Yu-Ting; Yu, Qian; An, Lin-Kun
• Is Part Of: Dyes and pigments. Volume 169(2019)
• Page Start: 45
• Page End: 50
• Publication Date: 2019-10
• Subjects: Tyrosyl-DNA phosphodiesterase -- Fluorescent probe -- DNA repair -- Inhibitor; Dyes and dyeing -- Periodicals; Pigments -- Periodicals; 667.2
• DOI: 10.1016/j.dyepig.2019.05.010
• Languages: English
• ISSNs: 0143-7208

Abstract

Abstract: Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a recently discovered enzyme specifically repairing DNA topoisomerase IB-mediated DNA damage, and is a rational anticancer target. Herein, we report the design and synthesis of the first small fluorescent probe 1 as TDP1 substrate. Probe 1 is a specific substrate of TDP1 and shows good spectroscopic properties with more than 140-fold fluorescence enhancement. A novel TDP1 inhibition assay was established using 1 as substrate. The possible cleavage pathway of 1 by TDP1 was also studied. Highlights: The first small fluorescent probe 1 as TDP1 substrate was synthesized. Probe 1 is a specific substrate of TDP1. Probe 1 shows more than 140-fold fluorescence enhancement. A novel screening assay for TDP1 inhibitors was established.