Transfer of 4'-chloro-2,2':6',2"-terpyridine platinum(II) between human serum albumin, glutathione and other thiolate ligands. A possible selective natural transport mechanism for the delivery of platinum(II) drugs to tumour cells.

Journal article

The antitrypanosomal and antitumour activities of (2,2':6',2"-terpyridine)platinum(II) complexes have been postulated to be due to their ability to inhibit irreversibly the NADPH/FAD redox enzymes trypanothione reductase and human thioredoxin reductase respectively. Here we show that these platinum(II) complexes metallate recombinant human albumin (rHA) at the single free thiol group (Cys-34). Moreover, the (2,2':6',2"-terpyridine)platinum(II) complex can be transferred from rHA to other thiols, such as 2-hydroxyethanethiol or glutathione. Human serum albumin could therefore provide a natural transport mechanism for the selective delivery of these agents to tumor cells by the enhanced permeability and retention (EPR) mechanism.

Authors: Ross, SA; Carr, C; Brïet, J; Lowe, G

• Publication status: Published
• Journal: Anti-cancer drug design
• Volume: 15
• Issue: 6
• Pages: 431-439
• Publication date: 2000-12-01
• EISSN: 1460-2148
• ISSN: 0266-9536
• Language: English
• Keywords: Spectrometry, Mass, Electrospray Ionization; Biological Transport; Recombinant Proteins; Sulfhydryl Compounds; Tumor Cells, Cultured; Glutathione; 2,2'-Dipyridyl; Spectrophotometry, Ultraviolet; Serum Albumin; Humans; Antineoplastic Agents; Organoplatinum Compounds; Magnetic Resonance Spectroscopy