一种强效葡萄糖-铂共轭物利用葡萄糖转运蛋白并优先在癌细胞中积累。
A Potent Glucose-Platinum Conjugate Exploits Glucose Transporters and Preferentially Accumulates in Cancer Cells.
作者信息
Patra Malay, Johnstone Timothy C, Suntharalingam Kogularamanan, Lippard Stephen J
机构信息
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Department of Chemistry, King's College London, London, SE1 1DB, UK.
出版信息
Angew Chem Int Ed Engl. 2016 Feb 12;55(7):2550-4. doi: 10.1002/anie.201510551. Epub 2016 Jan 8.
Abstract
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.
摘要
合成了三种合理设计的葡萄糖 - 铂共轭物（Glc - Pts）并评估了它们的生物活性。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。为了进入细胞，Glc - Pt 1利用了葡萄糖转运蛋白和有机阳离子转运蛋白，这两种转运蛋白在癌细胞中均广泛过度表达。与正常上皮细胞相比，化合物1在体外优先在癌细胞中积累并消灭癌细胞。
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