Selective ablation of β-galactosidase-expressing cells with a rationally designed activatable photosensitizer

Yuki Ichikawa, Mako Kamiya, Fumiaki Obata, Masayuki Miura, Takuya Terai, Toru Komatsu, Tasuku Ueno, Kenjiro Hanaoka, Tetsuo Nagano, Yasuteru Urano

研究成果: Article査読

97 被引用数 (Scopus)

抄録

We have developed an activatable photosensitizer capable of specifically inducing the death of β-galactosidase-expressing cells in response to photoirradiation. By using a selenium-substituted rhodol scaffold bearing β-galactoside as a targeting substituent, we designed and synthesized HMDESeR-βGal, which has a non-phototoxic spirocyclic structure owing to the presence of the galactoside moiety. However, β-galactosidase efficiently converted HMDESeR-βGal into phototoxic HMDESeR, which exists predominantly in the open xanthene form. This structural change resulted in drastic recovery of visible-wavelength absorption and the ability to generate singlet oxygen (1O2). When HMDESeR-βGal was applied to larval Drosophila melanogaster wing disks, which express β-galactosidase only in the posterior region, photoirradiation induced cell death in the β-galactosidase-expressing region with high specificity. Bull's eye! An activatable photosensitizer capable of specifically inducing the death of β-galactosidase-expressing cells in response to light irradiation was developed. Reaction with the enzyme resulted in a dynamic structural change to the phototoxic open form (see scheme), thus enabling the specific ablation of cells of interest in living tissues.

本文言語English
ページ(範囲)6772-6775
ページ数4
ジャーナルAngewandte Chemie - International Edition
53
26
DOI
出版ステータスPublished - 2014 6月 23
外部発表はい

ASJC Scopus subject areas

  • 触媒
  • 化学一般

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