Selective photoinactivation of protein function through environment-sensitive switching of singlet oxygen generation by photosensitizer

Takatoshi Yogo, Yasuteru Urano, Akiko Mizushima, Hisato Sunahara, Takanari Inoue, Kenzo Hirose, Masamitsu Iino, Kazuya Kikuchi, Tetsuo Nagano

Research output: Contribution to journalArticlepeer-review

Abstract

Chromophore-assisted light inactivation is a promising technique to inactivate selected proteins with high spatial and temporal resolution in living cells, but its use has been limited because of the lack of a methodology to prevent nonspecific photodamage in the cell owing to reactive oxygen species generated by the photosensitizer. Here we present a design strategy for photosensitizers with an environment-sensitive off/on switch for singlet oxygen (1O2) generation, which is switched on by binding to the target, to improve the specificity of protein photoinactivation. 1O2 generation in the unbound state is quenched by photoinduced electron transfer, whereas 1O2 generation can occur in the hydrophobic environment provided by the target protein, after specific binding. Inositol 1,4,5-trisphosphate receptor, which has been suggested to have a hydrophobic pocket around the ligand binding site, was specifically inactivated by an environment-sensitive photosensitizer-conjugated inositol 1,4,5-trisphosphate receptor ligand without 1O2 generation in the cytosol of the target cells, despite light illumination, demonstrating the potential of environment-sensitive photosensitizers to allow high-resolution control of generation of reactive oxygen species in the cell.

Original languageEnglish (US)
Pages (from-to)28-32
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number1
DOIs
StatePublished - Jan 8 2008
Externally publishedYes

Keywords

  • Activatable photosensitizer
  • Boron dipyrromethene derivative
  • Electron transfer
  • Inositol 1,4,5-trisphosphate receptor

ASJC Scopus subject areas

  • General

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