Thiols oxidation and covalent binding of BSA by cyclolignanic quinones are enhanced by the magnesium cation

Abstract

A novel cyclolignanic quinone, 7-acetyl-3′,4′-didemethoxy-3′,4′-dioxopodophyllotoxin (CLQ), inhibits topoisomerase II (TOPO II) activity. The extent of this inhibition was greater than that produced by the etoposide quinone (EQ) or etoposide. Glutathione (GSH) reduces EQ and CLQ to their corresponding semiquinones under anaerobic conditions. The latter were detected by EPR spectroscopy in the presence of MgCl 2 but not in its absence. Semiquinone EPR spectra change with quinone/GSH mol ratio, suggesting covalent binding of GSH to the quinones. Quinone-GSH covalent adducts were isolated and identified by ESI-MS. These orthoquinones also react with nucleophilic groups from BSA to bind covalently under anaerobic conditions. BSA thiol consumption and covalent binding by these quinones are enhanced by MgCl 2 . Complex formation between the parent quinones and Mg +2 was also observed. Density functional calculations predict the observed blueshifts in the absorption spectra peaks and large decreases in the partial negative charge of electrophilic carbons at the quinone ring when the quinones are complexed to Mg +2 . These observations suggest a possible role of Mg +2 chelation by these quinones in increasing TOPO II thiol and/or amino/imino reactivity with these orthoquinones.

Effect of Plant Extracts on Lipid Oxidation and Changes in Nutritive Value of Protein in Frozen-Stored Meat Products

“…Alegria et al . () reported that the above‐maintained adducts were also identified for BSA in presence of cyclolignanic quinones. Furthermore, the covalent binding of orthoquinones to BSA is mediated by both thiol groups and amino or imino groups.…”

Effect of white grape extract and modified atmosphere packaging on lipid and protein oxidation in chill stored beef patties

“…In wine production, the addition of glutathione reduces the browning of wine caused by oxidation of phenols by forming thiol-quinone adducts, where especially, ortho-phenolic structures as present in (+)-catechin or (À)-epicatechin are highly susceptible to adduct formation with nucleophile thiols (Singleton & Cilliers, 1995). The adduct has been identified for several proteins including BSA, a-lactalbumin, and lysosome (Alegria et al, 2008;Prigent, Voragen, Visser, van Koningsveld, & Gruppen, 2007). A similar reaction could be important for beef with plant phenols added as antioxidants, and such reactions are currently studied.…”

Protein oxidation in muscle foods: A review

“…Addition of glutathione reduces the browning of wine caused by oxidation of phenols by forming thiol‐quinone adducts 95, and the adduct has been identified for several proteins e.g . BSA 96. A similar reaction could be important for muscle foods with plant phenols added as anti‐oxidants, and such reactions are currently being studied.…”