Reactions of trimethylphosphine analogues of auranofin with bovine serum albumin

Journal Article · Wed Oct 05 00:00:00 EDT 1988 · Inorg. Chem.; (United States)

DOI:https://doi.org/10.1021/ic00293a029· OSTI ID:6232413

Isab, A A; Shaw, III, C F; Hoeschele, J D; Locke, J

The reactions of bovine serum albumin (BSA) with (trimethylphosphine)(2,3,4,6-tetra-O-acetyl-1-thio-..beta..-D-glucopyranosato-S)gold(I), Me/sub 3/PAuSAtg, and its chloro analogue, Me/sub 3/PAuCl, were studied to develop insights into the role of the phosphine ligand in the serum chemistry of the related antiarthritic drug auranofin (triethylphosphine)(2,3,4,6-tetra-O-acetyl-1-thio-..beta..-D-glucopyranosato-S)gold(I). /sup 31/P NMR spectroscopy, protein modification, and gel-exclusion chromatography methods were employed. Comparison of the reactions of the methyl derivatives to the previously reported reactions of auranofin and Et/sub 3/PAuCl with BSA demonstrated that similar chemical species are formed but revealed three major differences. Despite these differences, the results for the methyl analogues provide important confirmation for previously developed chemical models of auranofin reactions in serum. Me/sub 3/PO was not observed in reaction mixtures lacking tetraacetylthioglucose (AtgSH); this result affirms the role of AtgSH, displaced by the reaction of Me/sub 3/PAuSAtg at Cys-34, in the generation of the phosphine oxide (an important metabolite in vivo). The weak binding sites on albumin react with Me/sub 3/PAuCl, but not Me/sub 3/PAuSAtg, demonstrating the importance of the strength and reactivity of the anionic ligand-gold bond on the reactions of auranofin analogues. The gold binding capacity of albumin is enhanced after Me/sub 3/PO is formed, consistent with reductive cleavage of albumin disulfide bonds by trimethylphosphine. 24 references, 2 figures, 3 tables.

• Research Organization: Univ. of Wisconsin, Milwaukee (USA)
• OSTI ID: 6232413
• Journal Information: Inorg. Chem.; (United States), Journal Name: Inorg. Chem.; (United States) Vol. 27:20; ISSN INOCA
• Country of Publication: United States
• Language: English

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
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Isotope Exchange
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54 ENVIRONMENTAL SCIENCES
ALBUMINS
ANIMALS
BLOOD SERUM
CATTLE
CHEMICAL REACTIONS
COMPLEXES
DATA
DISEASES
DOMESTIC ANIMALS
DRUGS
EXPERIMENTAL DATA
GOLD COMPLEXES
INFORMATION
ISOTOPES
LIGHT NUCLEI
MAMMALS
NMR SPECTRA
NUCLEI
NUMERICAL DATA
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PHOSPHINES
PHOSPHORUS 31
PHOSPHORUS COMPOUNDS
PHOSPHORUS ISOTOPES
PROTEINS
RHEUMATIC DISEASES
RUMINANTS
SKELETAL DISEASES
SPECTRA
STABLE ISOTOPES
TRANSITION ELEMENT COMPLEXES
VERTEBRATES