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Zinc is essential but toxic in excess. Bacterial metallothionein, SmtA from Synechococcus PCC 7942, sequesters and detoxifies four zinc ions per molecule and contains a zinc finger structurally similar to eukaryotic GATA. The dearth of other reported bacterial metallothioneins has been surprising. Here we describe related bacterial metallothioneins (BmtA)(More)
Acetaminophen and its glucuronide, sulfate, N-acetyl-L-cysteinyl, and L-cysteinyl metabolites can be rapidly detected by 1H NMR spectroscopy of intact, untreated human urine. Study of the time course of excretion of these metabolites in five clinically normal men after ingestion of the usual 1-g therapeutic dose of the drug showed that the mean 24-h(More)
This work is the first in-depth study of osmium binding to DNA and confirms the pharmacological activity of a new class of anticancer metallodrugs. We investigated the interactions between the potential biological target DNA and four osmium(II) arene complexes, of the type [(eta 6-arene)Os(LL)Cl]n+, where arene = biphenyl or p-cymene and LL =(More)
DNA has a strong affinity for many heterocyclic aromatic dyes, such as acridine and its derivatives. Lerman in 1961 first proposed intercalation as the source of this affinity, and this mode of DNA binding has since attracted considerable research scrutiny. Organic intercalators can inhibit nucleic acid synthesis in vivo, and they are now common anticancer(More)
Reactions of cisplatin (cis-[PtCl2(NH3)2]) with albumin are thought to play an important role in the metabolism of this anticancer drug. They are investigated here via (i) labeling of cisplatin with 15N and use of two-dimensional 1H,15N NMR spectroscopy, (ii) comparison of natural human serum albumin with recombinant human albumin (higher homogeneity and SH(More)
Inhibition of the growth of the human ovarian cancer cell line A2780 by organometallic ruthenium(II) complexes of the type [(eta(6)-arene)Ru(X)(Y)(Z)], where arene is benzene or substituted benzene, X, Y, and Z are halide, acetonitrile, or isonicotinamide, or X,Y is ethylenediamine (en) or N-ethylethylenediamine, has been investigated. The X-ray crystal(More)
Quantitative changes in the urinary excretion patterns of low molecular weight compounds were followed for up to 30 days after dosing of adult Sprague-Dawley rats with single intraperitoneal injections of CdCl2 (6-24 mumol/kg), using high resolution 1H NMR multicomponent urinalysis. There was a marked reduction in the rate of urinary excretion of citrate,(More)
Rats were injected intraperitoneally with HgCl2 at doses of 2.5, 5, 7.5, and 10 mumol of Hg/kg. Urine was collected over a 24-hr period. At this time, plasma samples were taken and kidney damage was assessed by histological examination. Urinary gamma-glutamyltransferase levels were significantly elevated at Hg2+ doses of 7.5 and 10 mumol/kg, consistent with(More)
Circular dichroism and electron spin resonance spectroscopy are used to investigate the second specific metal binding site on human, bovine and porcine albumins. Ni(II), Zn(II) and Cd(II) can displace Cu(II) from the second Cu(II) site but not from the first strong site of human and bovine albumins (the N-terminal site). The second Cu(II) binds more(More)
1. Reactions of fatty-acid-free bovine serum albumin and recombinant human albumin with a range of antiarthritic gold(I) complexes [auranofin, deacetylated auranofin, triethylphosphinegold(I) chloride] and related thiols (thioglucose, tetraacetylthioglucose, glutathione, dithiothreitol) have been investigated using 1H-NMR spectroscopy. 2. In reactions of(More)