Patra Malay, Johnstone Timothy C, Suntharalingam Kogularamanan, Lippard Stephen J
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Department of Chemistry, King's College London, London, SE1 1DB, UK.
Angew Chem Int Ed Engl. 2016 Feb 12;55(7):2550-4. doi: 10.1002/anie.201510551. Epub 2016 Jan 8.
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.
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。
