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.