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Title: Reactions of trimethylphosphine analogues of auranofin with bovine serum albumin

Abstract

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 bymore » trimethylphosphine. 24 references, 2 figures, 3 tables.« less

Authors:
; ; ;
Publication Date:
Research Org.:
Univ. of Wisconsin, Milwaukee (USA)
OSTI Identifier:
6232413
Resource Type:
Journal Article
Journal Name:
Inorg. Chem.; (United States)
Additional Journal Information:
Journal Volume: 27:20
Country of Publication:
United States
Language:
English
Subject:
54 ENVIRONMENTAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL AND ANALYTICAL CHEMISTRY; ALBUMINS; CHEMICAL REACTIONS; BLOOD SERUM; DRUGS; GOLD COMPLEXES; PHOSPHINES; CATTLE; EXPERIMENTAL DATA; NMR SPECTRA; PHOSPHORUS 31; RHEUMATIC DISEASES; ANIMALS; COMPLEXES; DATA; DISEASES; DOMESTIC ANIMALS; INFORMATION; ISOTOPES; LIGHT NUCLEI; MAMMALS; NUCLEI; NUMERICAL DATA; ODD-EVEN NUCLEI; ORGANIC COMPOUNDS; PHOSPHORUS COMPOUNDS; PHOSPHORUS ISOTOPES; PROTEINS; RUMINANTS; SKELETAL DISEASES; SPECTRA; STABLE ISOTOPES; TRANSITION ELEMENT COMPLEXES; VERTEBRATES; 500600* - Environment, Atmospheric- Regulations- (-1989); 400202 - Isotope Effects, Isotope Exchange, & Isotope Separation

Citation Formats

Isab, A A, Shaw, III, C F, Hoeschele, J D, and Locke, J. Reactions of trimethylphosphine analogues of auranofin with bovine serum albumin. United States: N. p., 1988. Web. doi:10.1021/ic00293a029.
Isab, A A, Shaw, III, C F, Hoeschele, J D, & Locke, J. Reactions of trimethylphosphine analogues of auranofin with bovine serum albumin. United States. https://doi.org/10.1021/ic00293a029
Isab, A A, Shaw, III, C F, Hoeschele, J D, and Locke, J. 1988. "Reactions of trimethylphosphine analogues of auranofin with bovine serum albumin". United States. https://doi.org/10.1021/ic00293a029.
@article{osti_6232413,
title = {Reactions of trimethylphosphine analogues of auranofin with bovine serum albumin},
author = {Isab, A A and Shaw, III, C F and Hoeschele, J D and Locke, J},
abstractNote = {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.},
doi = {10.1021/ic00293a029},
url = {https://www.osti.gov/biblio/6232413}, journal = {Inorg. Chem.; (United States)},
number = ,
volume = 27:20,
place = {United States},
year = {Wed Oct 05 00:00:00 EDT 1988},
month = {Wed Oct 05 00:00:00 EDT 1988}
}