Glutathione analogs

Design and synthesis of glutathione analogs containing heterocyclic fragments 98F721. 

Soglia, J. R., Contillo, L. G., Kalgutkar, A. S., Zhao, S., Hop, C. E. C. A., Boyd, J. G., and Cole, M. J. (2006). A semiquantitative method for the determination of reactive metabolite conjugate levels in vitro utilizing liquid chromatography-tandem mass spectrometry and novel quaternary ammonium glutathione analogs. Chem. Res. Toxicol. 19 480-490. 

Manual Solid-Phase Synthesis of Glutathione Analogs... 

This chapter provides a manual for a laboratory-hased short course to introduce the common techniques of solid-phase peptide synthesis (SPPS). The course provides students the opportunity to design and manually synthesize analogs of glutathione using relatively simple equipment available in any unsophisticated laboratory. The manual provides compact protocols for both the different steps of SPPS and the final cleavage of peptides from resin supports. We also introduce a simple method for the synthesis of combinatorial libraries of glutathione analogs that is suitable for those relatively unfamiliar with the field of peptide chemistry. 

It is important to further develop the concept of structure-activity relationships to precisely define the structural requirements of glutathione action. Thus, this section introduces the design, synthesis, and screening of a peptide combinatorial library to obtain multiple glutathione analogs. Combinatorial libraries will be composed of mixtures of peptides (consisting of natural or noncoded amino acids) on solid support. After cleavage from the resin, the mixtures of the peptides will be screened directly in different specific assays. 

Yamamoto, M., Sakamoto, N., Iwai, A., et al. (1993) Protective actions of YM737, a new glutathione analog, against cerebral ischemia in rats. Res. Commun. Chem. Pathol. Pharmacol. 81, 221—232. 

Kannan R, Bao Y, Wang Y, Sarthy VP, Kaplowitz N (1999) Protection from oxidant injury by sodium-depen dent GSH uptake in retinal Muller cells. Exp Eye Res 68 609-16 Kannan R, Chakrabarti R, Tang D, Kim KJ, Kaplowitz N (2000) GSH transport in human cerebrovascular endothelial cells and human astrocytes evidence for luminal localization of Na -dependent GSH transporter in HCEC. Brain Res 852 374-82 Kannan R, Kuhlenkamp JF, Ookhtens M, Kaplowitz N (1992) Transport of glutathione at blood-brain barrier of the rat inhibition by glutathione analogs and age-dependence. J Pharmacol Exp Ther 263 964-70... 

LeBlanc, A., Shiao, T.C., Roy, R., Sleno, L. (2010) Improved Detection of Reactive Metabolites with a Bromine-containing Glutathione Analog Using Mass Defect and Isotope Pattern Matching. Rapid Commun. Mass Spectrom. 24 1241-1250. 

Hollingworth RM, Alstott RL, Litzenberg RD. 1973. Glutathione-S-aryl transferase in the metabolism of parathion and its analogs. Life Sci 13 191 -199. 

The degradation of vinyl chloride and ethene has been examined in Mycobacterium sp. strain JS 60 (Coleman and Spain 2003) and in Nocardioides sp. strain JS614 (Mattes et al. 2005). For both substrates, the initially formed epoxides underwent reaction with reduced coenzyme M and, after dehydrogenation and formation of the coenzyme A esters, reductive loss of coenzyme M acetate resulted in the production of 5-acetyl-coenzyme A. The reductive fission is formally analogous to that in the glutathione-mediated reaction. 

Roberts, J. and Shaw, C.F. Ill (1998) Inhibition of erythrocyte selenium-glutathione peroxidase by auranofin analogs and metabolites. Biochemical Pharmacology, 55, 1291-1299. 

In an analogous reaction catalyzed by 2,5-dihydroxypyridine 5,6-dioxygenases from various strains (Scheme 3d), the hydrolysis products maleamate and formate were identified. The latter enzymes require Fe2+ and a thiol donor such as dithiothreitol, cysteine, or glutathion for activity. 

It is not clear whether V(V) or V(IV) (or both) is the active insulin-mimetic redox state of vanadium. In the body, endogenous reducing agents such as glutathione and ascorbic acid may inhibit the oxidation of V(IV). The mechanism of action of insulin mimetics is unclear. Insulin receptors are membrane-spanning tyrosine-specific protein kinases activated by insulin on the extracellular side to catalyze intracellular protein tyrosine phosphorylation. Vanadates can act as phosphate analogs, and there is evidence for potent inhibition of phosphotyrosine phosphatases (526). Peroxovanadate complexes, for example, can induce autophosphorylation at tyrosine residues and inhibit the insulin-receptor-associated phosphotyrosine phosphatase, and these in turn activate insulin-receptor kinase. 

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