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Selective Ablation of β‐Galactosidase‐Expressing Cells with a Rationally Designed Activatable Photosensitizer
Author(s) -
Ichikawa Yuki,
Kamiya Mako,
Obata Fumiaki,
Miura Masayuki,
Terai Takuya,
Komatsu Toru,
Ueno Tasuku,
Hanaoka Kenjiro,
Nagano Tetsuo,
Urano Yasuteru
Publication year - 2014
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201403221
Subject(s) - photosensitizer , chemistry , phototoxicity , singlet oxygen , xanthene , galactoside , moiety , substituent , drosophila melanogaster , biophysics , photochemistry , microbiology and biotechnology , biochemistry , stereochemistry , oxygen , in vitro , biology , enzyme , organic chemistry , gene
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 ( 1 O 2 ). 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.