Biochemistry of Gold Drugs

The vast majority of intravascular gold is protein bound, and most of this ( 85%) is bound to albumin, with the remainder linked to globulin moieties. Gold complexes bind to many proteins with inhibition of activity, and the reactions have been extensively tabulated [10]. Studies on bovine serum albumin (BSA) confirmed, both for AuSTM and AF, that the binding site was the unique cysteine residue, Cys34 [31, 32, 33]. The PEt3 of AF is not lost [32, 33] and the reaction is best considered as a thiol displacement  

With AuSTM, the major strong binding product is indicated to have a AuS2 binding core  

Weaker binding occurs, either via bridging thiomalates or noncovalent interactions and models for these have been proposed [31]. 

Mechanisms whereby the polymeric AuSTM, and presumably AuTG, are broken down to react with albumin in an essentially monomeric form come from studies on the reactions of these complexes with low molecular weight thiols. NMR studies showed slow exchange between AuSTM and thiomalate, A-acetylcysteine, mercaptoacetate and glutathione [34, 35]. 

Similarly, a five-fold excess of cysteine can displace thiomalate at 100 / M concentrations [36]. The bis(ligand) complexes, Au(Cys)J and (Cys) AuSTM have been indicated as the products of these reactions [36—38], although small clusters of the type [Au4(SR)7]or of stoichiometry Au(SR)i 75 have also been proposed [34, 35]. Gold thiolate chemistry is covered in reviews [9—11], and more details on Au(I) and Au compounds are presented in ref. [39]. 

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