Selective Ablation of β-Galactosidase-Expressing Cells with a Rationally Designed Activatable Photosensitizer
Selective Ablation of β-Galactosidase-Expressing Cells with a Rationally Designed Activatable Photosensitizer
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DOI：
10.1002/anie.201403221
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发表时间：
2014-06-01
影响因子：
16.6
通讯作者：
Urano, Yasuteru
中科院分区：
文献类型：
--
作者：
Ichikawa, Yuki;Kamiya, Mako;Urano, Yasuteru
我们已经开发了一种可活化的光敏剂，能够特异性诱导表达β-半乳糖苷酶的细胞响应于光照射而死亡。通过使用硒取代的rhodol支架轴承β-半乳糖苷作为靶向取代基，我们设计和合成HMDESeR-β Gal，它具有非光毒性螺环结构，由于半乳糖苷部分的存在。然而，β-半乳糖苷酶有效地将HMDESeR-β Gal转化为光毒性HMDESeR，其主要以开放的咕吨形式存在。这种结构变化导致可见波长吸收和产生单线态氧（O-1（2））的能力急剧恢复。当HMDESeR-β半乳糖苷酶被施加到幼虫果蝇翅盘，只在后部区域表达β-半乳糖苷酶，光照射诱导细胞死亡的β-半乳糖苷酶表达区域具有高度特异性。
We have developed an activatable photosensitizer capable of specifically inducing the death of beta-galactosidase-expressing cells in response to photoirradiation. By using a selenium-substituted rhodol scaffold bearing beta-galactoside as a targeting substituent, we designed and synthesized HMDESeR-beta Gal, which has a non-phototoxic spirocyclic structure owing to the presence of the galactoside moiety. However, beta-galactosidase efficiently converted HMDESeR-beta Gal 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 (O-1(2)). When HMDESeR-beta Gal was applied to larval Drosophila melanogaster wing disks, which express beta-galactosidase only in the posterior region, photoirradiation induced cell death in the beta-galactosidase-expressing region with high specificity.