A Potent Glucose-Platinum Conjugate Exploits Glucose Transporters and Preferentially Accumulates in Cancer Cells.
A Potent Glucose-Platinum Conjugate Exploits Glucose Transporters and Preferentially Accumulates in Cancer Cells.
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DOI：
10.1002/anie.201510551
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发表时间：
2016-02-12
期刊：
影响因子：
--
通讯作者：
Lippard SJ
中科院分区：
文献类型：
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作者：
Patra M;Johnstone TC;Suntharalingam K;Lippard SJ
设计合成了三种葡萄糖铂偶联物（Glc-Pts），并对其生物活性进行了评价。Glc-Pts 1-3对一组癌细胞表现出高水平的细胞毒性。阐明了Glc-Pts的亚细胞靶点和细胞摄取机制。为了摄取到细胞中，Glc-Pt 1利用葡萄糖和有机阳离子转运蛋白两者，这两者在癌症中广泛过表达。在体外，与正常上皮细胞相比，化合物1优先在癌细胞中积累并消灭癌细胞。
Three rationally designed glucose-platinum conjugates (Glc-Pts) were synthesized and their biological activities evaluated. The Glc-Pts, 1-3, exhibit high levels of cytotoxicity toward a panel of cancer cells. The subcellular target and cellular uptake mechanism of the Glc-Pts were elucidated. For uptake into cells, Glc-Pt 1 exploits both glucose and organic cation transporters, both widely overexpressed in cancer. Compound 1 preferentially accumulates in and annihilates cancer, compared to normal epithelial, cells in vitro.