Selective photoinactivation of protein function through environment-sensitive switching of singlet oxygen generation by photosensitizer
| Autor: | Hisato Sunahara, Yasuteru Urano, Tetsuo Nagano, Kenzo Hirose, Takanari Inoue, Masamitsu Iino, Akiko Mizushima, Takatoshi Yogo, Kazuya Kikuchi |
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| Rok vydání: | 2008 |
| Předmět: |
Boron Compounds
Light Photochemistry Porphobilinogen Plasma protein binding Models Biological Photoinduced electron transfer Cell Line chemistry.chemical_compound Cytosol Animals Inositol 1 4 5-Trisphosphate Receptors Photosensitizer Boron Fluorescent Dyes chemistry.chemical_classification Reactive oxygen species Multidisciplinary Photosensitizing Agents Singlet Oxygen Singlet oxygen Ligand (biochemistry) Oxygen chemistry Physical Sciences Target protein Chickens Protein Binding |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 105(1) |
| ISSN: | 1091-6490 |
| Popis: | 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 ( 1 O 2 ) generation, which is switched on by binding to the target, to improve the specificity of protein photoinactivation. 1 O 2 generation in the unbound state is quenched by photoinduced electron transfer, whereas 1 O 2 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 1 O 2 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. |
| Databáze: | OpenAIRE |
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