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
Ross, S.A.; Carr, C.A.; Brïet, J.W.; Lowe, G.
Anti-Cancer Drug Design 15(6): 431-439
2000
ISSN/ISBN: 0266-9536 PMID: 11716436 Document Number: 521086
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.