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ESI MS studies highlight the selective interaction of Auranofin with protein free thiols.
Dalton Trans. 2020 May 14; 49(18):5906-5913.DT

Abstract

The clinically established gold drug Auranofin was reacted individually with a group of representative proteins, namely ubiquitin, ribonuclease A, carbonic anhydrase, haemoglobin and superoxide dismutase, and adduct formation was monitored in the various cases by ESI-MS analysis. We found that the reaction is highly selective for solvent exposed free cysteines that are modified through coordination of the AuPEt3+ fragment. Indeed, ESI-Q-TOF MS spectra carried out on protein samples incubated with a three fold molar excess of Auranofin allowed direct detection of the native proteins bearing bound AuPEt3+ fragments in the cases of carbonic anhydrase and haemoglobin. At variance, the two proteins that do not possess any free cysteine residue, i.e. ubiquitin and ribonuclease A, were unable to bind the gold fragment. In the case of superoxide dismutase, adduct formation is hindered by the scarce solvent accessibility of the free cysteine residue. These findings were further confirmed by a series of competition binding experiments with ebselen, a potent and selective cysteine-modifying reagent; we observed that pre-treatment with ebselen prevents the binding of the AuPEt3+ fragment to both carbonic anhydrase and haemoglobin.

Authors+Show Affiliations

Laboratory of Metals in Medicine (MetMed), Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 3-13, 50019 Sesto Fiorentino, Italy. luigi.messori@unifi.it.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32314767

Citation

Zoppi, Carlotta, et al. "ESI MS Studies Highlight the Selective Interaction of Auranofin With Protein Free Thiols." Dalton Transactions (Cambridge, England : 2003), vol. 49, no. 18, 2020, pp. 5906-5913.
Zoppi C, Messori L, Pratesi A. ESI MS studies highlight the selective interaction of Auranofin with protein free thiols. Dalton Trans. 2020;49(18):5906-5913.
Zoppi, C., Messori, L., & Pratesi, A. (2020). ESI MS studies highlight the selective interaction of Auranofin with protein free thiols. Dalton Transactions (Cambridge, England : 2003), 49(18), 5906-5913. https://doi.org/10.1039/d0dt00283f
Zoppi C, Messori L, Pratesi A. ESI MS Studies Highlight the Selective Interaction of Auranofin With Protein Free Thiols. Dalton Trans. 2020 May 14;49(18):5906-5913. PubMed PMID: 32314767.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - ESI MS studies highlight the selective interaction of Auranofin with protein free thiols. AU - Zoppi,Carlotta, AU - Messori,Luigi, AU - Pratesi,Alessandro, Y1 - 2020/04/21/ PY - 2020/4/22/pubmed PY - 2020/4/22/medline PY - 2020/4/22/entrez SP - 5906 EP - 5913 JF - Dalton transactions (Cambridge, England : 2003) JO - Dalton Trans VL - 49 IS - 18 N2 - The clinically established gold drug Auranofin was reacted individually with a group of representative proteins, namely ubiquitin, ribonuclease A, carbonic anhydrase, haemoglobin and superoxide dismutase, and adduct formation was monitored in the various cases by ESI-MS analysis. We found that the reaction is highly selective for solvent exposed free cysteines that are modified through coordination of the AuPEt3+ fragment. Indeed, ESI-Q-TOF MS spectra carried out on protein samples incubated with a three fold molar excess of Auranofin allowed direct detection of the native proteins bearing bound AuPEt3+ fragments in the cases of carbonic anhydrase and haemoglobin. At variance, the two proteins that do not possess any free cysteine residue, i.e. ubiquitin and ribonuclease A, were unable to bind the gold fragment. In the case of superoxide dismutase, adduct formation is hindered by the scarce solvent accessibility of the free cysteine residue. These findings were further confirmed by a series of competition binding experiments with ebselen, a potent and selective cysteine-modifying reagent; we observed that pre-treatment with ebselen prevents the binding of the AuPEt3+ fragment to both carbonic anhydrase and haemoglobin. SN - 1477-9234 UR - https://www.unboundmedicine.com/medline/citation/32314767/ESI_MS_studies_highlight_the_selective_interaction_of_Auranofin_with_protein_free_thiols L2 - https://doi.org/10.1039/d0dt00283f DB - PRIME DP - Unbound Medicine ER -
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