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- W2147804945 abstract "Correspondence: David S. Goodsell, Ph.D., The Scripps Research Institute, Department of Molecular Biology, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. Telephone: 858-784-2839; Fax: 858-784-2860; e-mail: goodsell@scripps.edu Web site: http://www.scripps.edu/pub/goodsell Received January 13, 2006; accepted for publication January 13, 2006. ©AlphaMed Press 10837159/2006/$20.00/0 Cisplatin provides a perfect example of how small changes in molecular structure can lead to profound differences in biological activity. It is a tiny molecule, composed of a platinum ion surrounded by four ligands arranged in a square. If you choose two amines and two chlorides as ligands, there are two ways to arrange them around the platinum ion. In cisplatin (Fig. 1), the chlorides are next to each other, and treatment with the compound can cure testicular cancer. If the chlorides are arranged opposite one other, however, the compound has no activity. The reason for this difference becomes apparent when you look at the cellular target of cisplatin. Inside a cell, cisplatin loses its two chloride ions, creating a reactive species that forms bonds with DNA bases. Because of the cis geometry of these bonds, cisplatin easily forms crosslinks between bases, as shown in Figure 2. Most of these crosslinks are formed at sites where guanine and adenine are next to each other in the same strand, but in some cases, cisplatin can form links between the two strands. As you might imagine, these crosslinks cause severe problems when the cell attempts to read or replicate its DNA." @default.
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- W2147804945 date "2006-03-01" @default.
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- W2147804945 title "The Molecular Perspective: Cisplatin" @default.
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- W2147804945 doi "https://doi.org/10.1634/stemcells.2006-csc2" @default.
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