Glutathione derivatives

After intraperitoneal administration of radiolabelled ethylene dibromide to guinea-pigs (30 mg/kg bw) or mice (40 mg/kg bw), the largest portion of the radioactivity was excreted in urine. The highest levels of radio activity were found in kidney, liver and stomach. Enzymatic reaction with glutathione (GSH) in vitro and in vivo as well as excretion of glutathione-derived metabolites in urine of rats and mice have been demonstrated (lARC, 1977). 

S,R)-glutathione derivative Fig. 4-30. Stereoselective four component condensation (4CC). 

The interaction of nine nucleobases (thymine, uracil, dihydrouracil, cytosine, adenine, guanine, diaminopurine, xanthine, hypoxanthine), in their deprotonated form, with zinc and with themselves in [Zn(nucleobase)(Tpph Me)] has been investigated. Selected compounds have been characterized by single-crystal X-ray study.158 Gelinski et al. reported the synthesis and characterization of two zinc complexes containing the ligand Tpph,Me and glutathione derivatives (Fig. 3.28).159... 

An A-acetylcysteine-melamine adduct (105) has been described as shown in Scheme 25. The mechanism probably involves a methyleneiminium ion (104). A-Hydroxymethyl compounds are produced by the metabolism of materials which contain A-methyl groups by preparations of murine liver. Hexamethylmelamine (HMM) is hydroxylated by this route, which involves cytochrome P450. As electrophiles, these A-hydroxymethyl compounds may be excreted as glutathione conjugates, hence (105) and other A-acetylcysteine and glutathione derivatives were prepared as part of a study of possible biochemical mechanisms <85JCS(Pi)75>. 

Hill et al. [456] separated, in <20 min, hydroquinone from four of its 5-substituted glutathione derivatives on a C g column (electrochemical 15-channel detector from —250 to -1-450 mV using glassy carbon) using a 6/94 methanol/water (4mM citric acid in 8mM ammonium acetate buffer at pH 4) mobile phase. Successful analyte detection down to the 1 pmol level was reported. Positive identification of the derivatives was done using a C g column (fast atom bombard-ment MS) and a 5/95 (93/7 methanol/glycerol)/([93/7 water/glycerol] with lOOmM ammonium acetate buffer at pH 5) mobile phase. 

Epoxy-activated agarose has been treated with 8-amino-xanthine and used to isolate urate oxidase. Escherichia coli lipopolysaccharide immobilized on epoxy-activated agarose provides an immunoadsorbent for isolation of antisera, and L-fucose immobilized on the same support may be used for the purification of L-fucose-specific lectins. Glutathione-agarose matrices prepared after epoxy-activation have been successfully applied to the purification of glutathione S -transferases. An 5-hexyl glutathione derivative similarly prepared has been used for purification of glyoxalase I from rabbit liver. 

Even in the earher considerations of the relation between SH and growth, some attempt was made to narrow the formulation of the problem. The SH activation of proteolytic enzymes was recognized in the early 1930 s. The notion of the reversibility of proteolytic enzymes is one that has been current for a long time and is still not without its advocates. It is therefore not at all siuprising that various workers (5, 10) should have stressed the possibility that the growth-stimulating action of glutathione derived from the activation of intracellular proteases in their postulated synthetic role. 

Chloroacetol phosphate alkylates the sulfhydryl group. ) The reaction mixture was cooled in an ice bath and then treated with a portion of the same stock solution of sodium [ Hjborohydride that was used in the reduction of the modified carboxylase (see above). The final borohydride concentration in the reaction mixture was 0.1 M. After 1 hr the mixture was acidified to pH 2.0 with 1 N HCl and chromatographed on a column (1.2 X 22 cm) of Dowex 50 (H ) equilibrated and eluted with 50 mAf HCl. The concentration of the glutathione derivative in the peak fraction was determined with the amino acid analyzer the radioactivity in the same fraction was also determined, thereby providing the specific radioactivity of the [ H] borohydride. 

In the F sediment under aerobic conditions, alachlor and compounds with Rf values of 0.7 and 0.55 were observed. Adding N or N+C, reduced the amount of radioactivity in these bands with more found as alachlor. Under anaerobic conditions, additional compounds were detected at 0.6 and 0.05. In sediment from the S zone, under saturated, aerobic conditions, compounds that cochromatographed with alachlor plus compounds at 0.6 and 0.45 were observed. Under anaerobic conditions, only the band that cochromatographed with alachlor was observed. The detection of ESA-alachlor in sediments under anaerobic conditions via the glutadiione-s-transferase enzyme would not be expected since oxygen for the oxidation of the glutathione-derived sulfur would be absent. 

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