Structural Characterization of a Gold/Serum Albumin Complex

Abstract

The medicinal gold(III) dithiocarbamato complex AuL12 forms a stable adduct with bovine serum albumin. The crystal structure reveals that a single gold(I) center is bound to Cys34, the dithiocarbamato ligand being released. To the best of our knowledge this is the first structure for a gold adduct of serum albumin.

Reactions of Medicinal Gold(III) Compounds With Proteins and Peptides Explored by Electrospray Ionization Mass Spectrometry and Complementary Biophysical Methods

“…AuL12 consists of a square-planar gold(III) center with a bidentate dithiocarbamate ligand and two bromide ligands. Notably, AuL12 was shown to behave as a prodrug upon releasing its bromide ligands (Pratesi et al, 2019). Significant oxidizing properties were also documented for this gold(III) complex (Nardon et al, 2017).…”

“…Upon reacting HSA with either Auxo6 or Au 2 phen, an apparent decrease in the overall quality of the ESI MS spectra is noticed, which is accompanied by a strong baseline distortion, with both tested stoichiometries (1:3 or 1:0.9 protein/metal ratio). In our previous experience, this behavior is quite common when dealing with metal complexes where the metal center is present in its higher oxidation state; probably this arises from the occurrence of a direct redox reaction between the metal complex and the biomolecule, leading to a plethora of minor adducts that are present in small amounts and are difficult to assign (Massai et al, 2019;Pratesi et al, 2019).…”

“…HSA is characterized by the presence of 17 disulfide bonds and only one free cysteine residue (Cys34) (Rombouts et al, 2015). Interestingly, the only free cysteine (Cys34) of HSA is solvent accessible and is considered the primary binding site for gold compounds owing to the high affinity of gold to sulfur-containing ligands (Pratesi et al, 2018(Pratesi et al, , 2019Zoppi et al, 2020).…”

“…This prompted investigators to analyze in detail the reactions of medicinal gold compounds with proteins. A systematic investigation on the interactions of the reference gold(I) drug auranofin with a series of model proteins, i.e., human serum albumin, carbonic anhydrase, superoxide dismutase, and hemoglobin, was recently carried out in our laboratory through mass spectrometry, and the resulting adducts could be characterized in molecular detail (Pratesi et al, 2016(Pratesi et al, , 2018(Pratesi et al, , 2019Magherini et al, 2018;Cirri et al, 2019;Zoppi et al, 2020). These studies revealed that auranofin targets quite selectively the free cysteine residues of proteins (Pratesi et al, 2018;Zoppi et al, 2020).…”

Mechanistic Insights Into the Anticancer Properties of the Auranofin Analog Au(PEt3)I: A Theoretical and Experimental Study

“…In fact, in some cases not all of these were able to highlight the adducts formation, requiring a further interrogation grounded on another instrumental method. His, Met, Cys, and Sec aminoacidic residues were selected since they are generally recognized as the likely binding site for the coordination of gold complexes to proteins in reason to their nature of soft ligands (Abhishek et al, 2019;Pratesi et al, 2019). Results reveal differences in the reaction profiles between AF and AF-I in particular toward both cysteine and selenocysteine while -in our experimental conditions-no reactivity occurs toward His and Met.…”