Gold-Protein Reactions and Complexes

This mechanism only requires [Au(CN)2] to be a highly transient metabolite , generated locally from administered gold drugs and in turn perhaps largely metabo-lized/decomposed locally. 

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These thiolate exchange reactions are thought to lead to incorporation of gold(I) to thiolate functions in proteins and enzymes, and thence to interfere with the inflammatory process. Thiols such as 2,3-dimercaptopropanol (BAL), iV-acetylcysteine and penicillamine have also been used in the treatment of gold toxicity. Protein-bound gold is mobilized by complexation to the added thiol and can then be excreted.250,273... 

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 ... 

These bis(thiolato)gold(I) complexes are useful models for providing insights into the chemistry of the end products of the reactions between 1 1 gold thiolates and any excess (including other) thiol, including some reactions with proteins in vivo. 

FIGURE 8.3 A hypothetical series of isomorphous heavy atom derivatives for a crystalline macromolecule, represented here by the polypeptide backbone of rubredoxin. (a) The apo-protein, stripped of its metal ion, provides native structure factors />, shown in vector and waveform on the right (b) the protein with its naturally bound iron atom and FHi, the first derivative structure factor (c) the protein with its iron plus an attached mercury atom, and the resultant structure factor Fm from the double derivative (d) a second multiply substituted derivative formed by attachment of a gold atom to the protein-iron complex. This last derivative is only marginally useful, however, since the reaction with gold also produces a modification in the tertiary structure of the protein (denoted by an arrow). Since this non-isomorphism is equivalent to introducing a nonnative structure factor contribution, the observed F s cannot be properly accounted for, and an erroneous heavy atom contribution / results. This final derivative will yield an inaccurate phase estimate 0v for the native protein. 

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