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

The antitrypanosomal and antitumour activities of (2,2':6',2"-terpyridine)p latinum(II) complexes have been postulated to be due to their ability to in hibit 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) co mplex can be transferred from rHA to other thiols, such as 2-hydroxyethanet hiol or glutathione. Human serum albumin could therefore provide a natural transport mechanism for the selective delivery of these agents to tumor cel ls by the enhanced permeability and retention (EPR) mechanism.