化学
兴奋剂
光电开关
体内
部分
腺苷
生物物理学
受体
体外
衍生工具(金融)
立体化学
生物化学
光化学
生物技术
金融经济学
经济
生物
作者
Marc López‐Cano,Mirko Scortichini,Dilip K. Tosh,Veronica Salmaso,Tongil Ko,Glòria Salort,Ingrid Filgaira,Concepció Soler,Dirk Trauner,Jordi Hernando,Kenneth A. Jacobson,Francisco Ciruela
摘要
Incorporating photoisomerizable moieties within drugs offers the possibility of rapid and reversible light-dependent switching between active and inactive configurations. Here, we developed a photoswitchable adenosine A3 receptor (A3R) agonist that confers optical control on this G protein-coupled receptor through noninvasive topical skin irradiation in an animal model of psoriasis. This was achieved by covalently bonding an adenosine-5′-methyluronamide moiety to a diazocine photochrome, whose singular photoswitching properties facilitated repeated interconversion between a thermally stable, biologically inactive Z agonist form and a photoinduced, pharmacologically active E configuration. As a result, our photoswitchable agonist allowed the precise modulation of A3R function both in vitro and in vivo, which led to a clear light-controlled pharmacotherapeutic effect on mouse skin lesions. This breakthrough not only demonstrates the potential of diazocine photoswitches for in vivo photopharmacology but also paves the way for the development of new strategies for skin-related diseases that require localized and temporally controlled drug action.
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