Inhibitory Effect of 8-Halogenated 7-Deaza-2′-deoxyguanosine Triphosphates on Human 8-Oxo-2′-deoxyguanosine Triphosphatase, hMTH1, Activities

Yizhen Yin, Shigeki Sasaki, Yosuke Taniguchi

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

hMTH1 (8-oxo-2′-deoxyguanine triphosphatase) hydrolyzes oxidized nucleoside triphosphates; its presence is non-essential for survival of normal cells but is required for survival of cancer cells. In this study, 8-halogenated-7-deaza-2′-deoxyguanosine triphosphate (8-halogenated-7-deazadGTP) derivatives were synthesized. Interestingly, these triphosphates were poor substrates for hMTH1, but exhibited strong competitive inhibition against hMTH1 at nanomolar levels. This inhibitory effect is attributed to slower rate of hydrolysis, possibly arising from enzyme structural changes, specifically different stacking interactions with 8-halogenated-7-deazadGTP. This is the first example of using nucleotide derivatives to inhibit hMTH1, thus demonstrating their potential as antitumor agents. New inhibitors: We synthesized triphosphate 8-halogenated-7-deazadG derivatives and showed their inhibitory effects on the human 8-oxo-2′-deoxyguanosine triphosphatase, hMTH1. These triphosphates are poor substrates for hMTH1, but exhibit strong competitive inhibition against hMTH1 at nanomolar levels. Therefore, they are candidates as novel antitumor agents.

Original languageEnglish
Pages (from-to)566-569
Number of pages4
JournalChemBioChem
Volume17
Issue number7
DOIs
Publication statusPublished - Apr 1 2016

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

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