کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1361350 | 981461 | 2008 | 9 صفحه PDF | دانلود رایگان |
The interaction of the well-known antitumor drug cisplatin cis-[PtCl2(NH3)2] and the compound trans-[PtCl2NH3(4-hydroxymethylpyridine)] with the small protein potato carboxypeptidase inhibitor (PCI) and a PCI mutant in which glycine-39 was substituted by methionine has been followed by HPLC/mass spectrometry. Our results showed that both Pt drugs were able to bind PCI through Met-39 and histidines in mutated PCI, whereas only the trans complex interacted significantly with wild PCI. In the cytotoxic studies, the monofunctional adduct PCI-Met–cisplatin was neither more active nor more selective than cisplatin itself when tested against three tumor cell lines with different number of EGF receptors. Those results suggested that the poor activity of the adduct could be just due to the small fraction of cisplatin which was decoordinated from the adduct and able to penetrate the tumor cells, as well as to the changes in the structure of the platinum drug after the loss of NH3 groups upon binding PCI-Met.
The binding of two platinum antitumor complexes to PCI protein (wild type and mutated) was proved by HPLC-MS and the cytotoxic activity of the adducts was measured by the typical MTT assay.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry - Volume 16, Issue 14, 15 July 2008, Pages 6832–6840