期刊
ACS CENTRAL SCIENCE
卷 5, 期 10, 页码 1676-1681出版社
AMER CHEMICAL SOC
DOI: 10.1021/acscentsci.9b00678
关键词
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资金
- AMED [JP19gm0710008, JP17gm0610004, JP19gm5010001]
- JST/PRESTO [JPMJPR14F8]
- MEXT/JSPS KAKENHI [JP16H02606, JP26111012, JP19H05632, JP15H05951, JP19H02826, JP19K22242, 16H06385]
- JSPS Core-to-Core Program
- Astellas Foundation for Research on Metabolic Disorders
- Japan Foundation for Applied Enzymology
- Japan Society for the Promotion of Science
- Grants-in-Aid for Scientific Research [16H06385] Funding Source: KAKEN
To achieve highly selective ablation of lacZ-positive cells in a biological milieu in vivo, we developed an activatable photosensitizer, SPiDER-killer-beta Gal, targeted to beta-galactosidase encoded by the lacZ reporter gene. Hydrolysis of SPiDER-killer-beta Gal by beta-galactosidase simultaneously activates both its photosensitizing ability and its reactivity to nucleophiles, so that the phototoxic products generated by light irradiation are trapped inside the lacZ-positive cells. The combination of SPiDER-killer-beta Gal and light irradiation specifically killed lacZ-positive cells in coculture with cells without lacZ expression. Furthermore, beta-galactosidase-expressing cells in the posterior region of cultured Drosophila wing discs and in pupal notum of live Drosophila pupae were selectively killed with single-cell resolution. This photosensitizer should be useful for specific ablation of targeted cells in living organisms, for example, to investigate cellular functions in complex networks.
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