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一种在耐药癌细胞中解码的治疗性键盘锁。

A therapeutic keypad lock decoded in drug resistant cancer cells.

作者信息

Turkoglu Gulsen, Koygun Gozde Kayadibi, Zafer Yurt Mediha Nur, Pirencioglu Seyda Nur, Erbas-Cakmak Sundus

机构信息

Department of Molecular Biology and Genetics, Konya Food and Agriculture University Meram Konya Turkey

Research and Development Center for Diagnostic Kits (KIT-ARGEM), Konya Food and Agriculture University Konya Turkey.

出版信息

Chem Sci. 2021 Jun 17;12(28):9754-9758. doi: 10.1039/d1sc02521j. eCollection 2021 Jul 21.

DOI:10.1039/d1sc02521j
PMID:34349948
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8293978/
Abstract

A molecular keypad lock that displays photodynamic activity when exposed to glutathione (GSH), esterase and light in the given order, is fabricated and its efficacy in drug resistant MCF7 cancer cells is investigated. The first two inputs are common drug resistant tumor markers. GSH reacts with the agent and shifts the absorption wavelength. Esterase separates the quencher from the structure, further activating the agent. After these sequential exposures, the molecular keypad lock is exposed to light and produces cytotoxic singlet oxygen. Among many possible combinations, only one 'key' can activate the agent, and initiate a photodynamic response. Paclitaxel resistant MCF7 cells are selectively killed. This work presents the first ever biological application of small molecular keypad locks.

摘要

制造了一种分子按键锁,当按给定顺序暴露于谷胱甘肽(GSH)、酯酶和光时,它会显示光动力活性,并研究了其在耐药MCF7癌细胞中的功效。前两个输入是常见的耐药肿瘤标志物。GSH与该试剂反应并改变吸收波长。酯酶将猝灭剂从结构中分离出来,进一步激活该试剂。在这些顺序暴露之后,分子按键锁暴露于光并产生细胞毒性单线态氧。在许多可能的组合中,只有一个“键”可以激活该试剂并引发光动力反应。耐紫杉醇的MCF7细胞被选择性杀死。这项工作首次展示了小分子按键锁的生物学应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87e5/8293978/0c7b0bdfce05/d1sc02521j-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87e5/8293978/4710ce6b1a38/d1sc02521j-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87e5/8293978/c7ba1c6eeca1/d1sc02521j-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87e5/8293978/8a0d0d58f9a2/d1sc02521j-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87e5/8293978/e8b8d461a17f/d1sc02521j-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87e5/8293978/fcccee463f04/d1sc02521j-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87e5/8293978/0c7b0bdfce05/d1sc02521j-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87e5/8293978/4710ce6b1a38/d1sc02521j-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87e5/8293978/c7ba1c6eeca1/d1sc02521j-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87e5/8293978/8a0d0d58f9a2/d1sc02521j-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87e5/8293978/e8b8d461a17f/d1sc02521j-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87e5/8293978/fcccee463f04/d1sc02521j-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87e5/8293978/0c7b0bdfce05/d1sc02521j-f6.jpg

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