Differential Effect of Azetidine Substitution in Firefly Luciferin Analogues

Yuma Ikeda, Mariko Orioka, Takahiro Nomoto, Yuki Hiruta, Nobuhiro Nishiyama, Daniel Citterio

Research output: Contribution to journalArticlepeer-review

Abstract

Replacing an N,N-dimethylamino group in a classical fluorophore with a four membered azetidine ring provides an improved luminescence quantum yield. Herein, we extended this strategy to bioluminescent firefly luciferin analogues and evaluated its general validity. For this purpose, four types of luciferin cores were employed, and a total of eight analogues were evaluated. Among these analogues, unexpectedly, only the benzothiazole core analogue benefited from an azetidine substitution and showed enhanced bioluminescence. In addition, fluorescence measurements revealed that an azetidine substitution improved the fluorescence quantum yield by 2.3-times compared to a N,N-dimethylamino group. These findings clarify the differential effects of azetidine substituents in luciferins and present one possible strategy for enhancing photon output in benzothiazole type luciferins through a synthetic approach.

Original languageEnglish
Pages (from-to)3067-3074
Number of pages8
JournalChemBioChem
Volume22
Issue number21
DOIs
Publication statusPublished - 2021 Nov 3

Keywords

  • enzyme catalysis
  • imaging agents
  • luciferins
  • luminescence
  • synthesis design

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

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