Bioinorganic and medicinal chemistry: aspects of gold(I)-protein complexes.

Abstract

Gold(I)-based drugs have been used successfully for the treatment of rheumatoid arthritis (RA) for several years. Although the exact mechanism of action of these gold(I) drugs for RA has not been clearly established, the interaction of these compounds with mammalian enzymes has been extensively studied. In this paper, we describe the interaction of therapeutic gold(I) compounds with mammalian proteins that contain cysteine (Cys) and selenocysteine (Sec) residues. Owing to the higher affinity of gold(I) towards sulfur and selenium, gold(I) drugs rapidly react with the activated cysteine or selenocysteine residues of the enzymes to form protein-gold(I)-thiolate or protein-gold(I)-selenolate complexes. The formation of stable gold(I)-thiolate/selenolate complexes generally lead to inhibition of the enzyme activity. The gold-thiolate/selenolate complexes undergo extensive ligand exchange reactions with other nucleophiles and such ligand exchange reactions alter the inhibitory effects of gold(i) complexes. Therefore, the effect of gold(I) compounds on the enzymatic activity of cysteine- or selenocysteine-containing proteins may play important roles in RA. The interaction of gold(I) compounds with different enzymes and the biochemical mechanism underlying the inhibition of enzymatic activities may have broad medicinal implications for the treatment of RA.

• Authors: Krishna P Bhabak, Bhaskar J Bhuyan, Govindasamy Mugesh
• Journal: Dalton transactions (Cambridge, England : 2003) (Dalton Trans) Vol. 40 Issue 10 Pg. 2099-111 (Mar 14 2011) ISSN: 1477-9234 [Electronic] England
• PMID: 21321730 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Coordination Complexes
• Proteins
• Serum Albumin
• Selenocysteine
• Gold
• Glutathione Reductase
• Protein Tyrosine Phosphatases
• Cysteine

Topics

• Arthritis, Rheumatoid (drug therapy)
• Binding Sites
• Catalytic Domain
• Chemistry, Pharmaceutical
• Coordination Complexes (chemistry, therapeutic use)
• Cysteine (chemistry)
• Glutathione Reductase (chemistry)
• Gold (chemistry)
• Humans
• Protein Tyrosine Phosphatases (chemistry)
• Proteins (chemistry)
• Selenocysteine (chemistry)
• Serum Albumin (chemistry)