期刊
JOURNAL OF INORGANIC BIOCHEMISTRY
卷 136, 期 -, 页码 161-169出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2014.01.009
关键词
Thioredoxin reductase; Gold NHC carbenes; Synthetic peptide; ESI-MS
资金
- Beneficentia Stiftung (Vaduz, Liechtenstein)
- Ente Cassa di Risparmio di Firenze
- Regione Toscana (NANO-TREAT project)
Gold-based drugs typically behave as strong inhibitors of the enzyme thioredoxin reductase (hTncR), possibly as the consequence of direct Gold(I) coordination to its active site selenocysteine. To gain a deeper insight into the molecular basis of enzyme inhibition and prove gold-selenocysteine coordination, the reactions of three parent Gold(I) NHC compounds with the synthetic C-terminal dodecapeptide of hTrxR containing Selenocysteine at position 498, were investigated by electrospray ionization mass spectrometry (ESI-MS). Formation of 1:1 Gold-peptide adducts, though in highly different amounts, was demonstrated in all cases. In these adducts the same [Au-NHC](+) moiety is always associated to the intact peptide. Afterward, tandem MS experiments, conducted on a specific Gold-peptide complex, pointed out that Gold is coordinated to the selenolate group. The relatively large strength of the Gold-selenolate coordinative bond well accounts for potent enzyme inhibition typically afforded by these Gold(I) compounds. In a selected case, the time course of enzyme inhibition was explored. Interestingly, enzyme inhibition turned out to show up very quickly and reached its maximum just few minutes after mixing. Overall, the present results offer some clear insight into the process of thioredoxin reductase inhibition by Gold-based compounds. (C) 2014 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据