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)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.
Ross
S A
SA
Department of Chemistry, University of Oxford, UK.
Carr
C A
CA
Brïet
J W
JW
Lowe
G
G
D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism*; D001692:Biological Transport; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D011994:Recombinant Proteins; D012709:Serum Albumin; D013438:Sulfhydryl Compounds; D015082:2,2'-Dipyridyl; D005978:Glutathione