ISSN:
1432-1327
Keywords:
Key words Dicyanoaurate(I)
;
Bovine serum albumin
;
Equilibrium binding constants
;
13C NMR
;
Labile dissociation
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
,
Chemistry and Pharmacology
Notes:
Abstract Dicyanoaurate(I), Au(CN)2 –, an important metabolite of chrysotherapy agents (anti-arthritic gold drugs), contains two tightly bound cyanide ligands which render it relatively unreactive toward ligand exchange reactions with potential gold-binding ligands. The extent and nature of its binding to bovine serum albumin (BSA), which may modulare the in vivo activity of Au(CN)2 –, were investigated to determine whether Au(CN)2 – might be more bioavailable than other gold complexes. 13C NMR spectroscopy, radioisotope tracers, chromatography, ultrafiltration, and atomic spectroscopy, employing Au(13CN)2 – or Au(14CN)2 – as appropriate, revealed two distinct binding mechanisms. The dominant reaction is reversible association (non-specific binding) of intact Au(CN)2 – ions to form BSA·[Au(CN)2 –] n adducts. Approximately one equivalent binds with an equilibrium binding constant (pH 7.4, 25 °C) of K 1=5.5 (±1.1)×104, and three additional equivalents bind with a constant of 7.0 (±0.1)×103. Au(13CN)2 – associated with albumin is characterized by a broad 13C NMR resonance at δC=154.7 ppm compared to the sharp resonance of the free complex at 156.4 ppm. The BSA·[Au(CN)2 –] n adducts readily dissociate during gel exclusion chromatography and are therefore underestimated, but are retained and accurately quantitated by ultrafiltration methods. The second binding mechanism is a ligand exchange reaction at Cys-34, to form AlbSAuCN, which accounts for only a small fraction (≤11%) of the bound gold. The small extent of the latter interaction differentiates Au(CN)2 – from the gold drugs such as auranofin, aurothiomalate (Myochrysin) and aurothioglucose (Solganol), which undergo ligand exchange at Cys-34 of albumin to form tightly bound gold-protein complexes. The weak interaction at Cys-34 and the facile dissociation of bound, intact Au(CN)2 – are consistent with its putative role as a gold metabolite that can be accumulated intracellularly.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s007750050203
Permalink
