Augmentation of human and rat lenticular glutathione in vitro by prodrugs of γ-L-glutamyl-L-cysteine

Journal of Medicinal Chemistry

Volumn 39, Issue 8, 1996, Pages 1676-1681

  Nagasawa, Herbert T ^a,b   Cohen, Jonathan F ^b   Holleschau, Ann M ^b   Rathbun, William B ^b  

^a VA MEDICAL CENTER   (United States)

^b UNIVERSITY OF MINNESOTA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GAMMA GLUTAMYLCYSTEINE; GAMMA GLUTAMYLCYSTEINE ETHYL ESTER; GLUTAMATE CYSTEINE LIGASE; GLUTATHIONE; PRODRUG; S ACETYL GAMMA GLUTAMYLCYSTEINE ETHYL ESTER; UNCLASSIFIED DRUG;

AGING; ANIMAL TISSUE; ARTICLE; CATARACT; CATARACTOGENESIS; CONTROLLED STUDY; DRUG MECHANISM; DRUG SYNTHESIS; ENZYME ACTIVITY; EYE PROTECTION; HUMAN; HUMAN TISSUE; LENS; NONHUMAN; OXIDATIVE STRESS; RAT; ULTRAVIOLET RADIATION;

ANIMALS; CATARACT; CHILD; DIPEPTIDES; GLUTATHIONE; HUMANS; LENS, CRYSTALLINE; PRODRUGS; RATS;

EID: 0030002899     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm950674y     Document Type: Article

References (32)

1. Reddy, V. N.; Giblin, F. J.; Matsuda, H. Defense system of the lens against oxidative damage. Red Blood Cell and Lens Metabolism; Srivastava, S. K., Ed.; Elsevier/North Holland: New York 1980; pp 139-154.
2. Deneke, S M.; Fanburg, B. L. Regulation of cellular glutathione. Am. J. Physiol. 1989, 257, L163-L173.
3. Murray, D. L.; Rathbun, W. B. Conditions for maximizing and inhibiting synthesis of glutathione in cultured rat lenses; an application of HPLC with radioisotope detection. Curr. Eye Res. 1990, 9, 55-63.
4. Rathbun, W. B.; Murray, D. L. Age-related cysteine uptake as rate-limiting in glutathione synthesis and glutathione half-life in the cultured human lens. Exp. Eye Res. 1991, 53, 205-212.
5. Rathbun, W. B. Glutathione synthesis in evolution: an Achilles' heel of human and other Old World simian lenses. Ophthal. Res. 1986, 18, 236-242.
6. Rathbun, W. B.; Holleschau, A. M.; Alterman, L. Glutathione metabolism in primate lenses: a phylogenetic study of glutathione synthesis and glutathione redox cycle enzyme activities. Am. J. Primatol. 1994, 33, 101-120.
7. Harding, J. J. Free and protein-bound glutathione in normal and cataractous human lenses. Biochem. J. 1970, 117, 957-960.
8. Rathbun, W. B. Activity of glutathione synthesis enzymes in the rhesus monkey lens related to age: a model for the human lens. Curr. Eye Res. 1986, 5, 161-166.
9. Sethna, S. S.; Holleschau, A. M.; Rathbun, W. B. Activity of glutathione synthesis enzymes in human lens related to age. Curr. Eye Res 1983, 2, 735-742.
10. Rathbun, W. B.; Holleschau, A. M. The effects of aging on glutathione synthesis enzymes in lenses of Old World simians and prosimians. Curr. Eye Res. 1992, 11, 601-607.
11. Ohtsu, A.; Kitahara, S.; Fujii, K. Agent for raising glutathione levels. Jpn. Pat. 64-26516, Jan. 27, 1989.
12. Ohtsu, A.; Kitahara, S.; Fujii, K. Anticataract properties of γ-glutamylcysteine ethyl ester in an animal model of cataract. Ophthal. Res. 1986, 18, 236-242.
13. Ohtsu, A.; Kitahara. S.; Fujii, K Anticataractogenic property of γ-glutamylcysteine ethyl ester in an animal model of cataract. Ophthal. Res. 1991, 23, 51-58.
14. Garst, M. E., Allergan, Inc., Irvine, CA. Personal communication.
15. Kahns, A. H.; Bundgaard. H. Prodrugs as drug delivery systems. 107. Synthesis and chemical and enzymatic hydrolysis kinetics of various mono- and diester prodrugs of N-acetylcysteine. Int. J. Pharm. 1990, 62, 193-205.
16. Elberling, J. A.; Zera, R. T.; Magnan, S. D. J.; Nagasawa, H. T. N-Phthaloyl-L-glutamic anhydride (2-phthalimidoglutaric anhydride). Org. Prep. Proc. Int. 1978, 11, 67-70.
17. Threadgill, M. D.; Gledhill, A. P. Synthesis of peptides containing S-(N-alkylcarbamoyl)cysteine residues, metabolites of N-alkylformamides in rodents and in humans. J. Org. Chem. 1989, 54, 2940-2949.
18. Nagasawa, H. T.; Magnan, S. D. J.; Foltz, R. L. Determination of α- from γ-glutamyl dipeptides by chemical ionization mass spectrometry. Biomed. Mass Spectrom. 1982, 9, 252-256.
19. Magnan, S. D. J.; Shirota, F. N.; Nagasawa, H. T. Drug latentiation by γ-glutamyltranspeptidase. J. Med. Chem. 1982, 25, 1018-1021.
20. Since this procedure involves carboxymethylation of the sulfhydryl group and dinitrophenylation of the free amino group, respectively, of GSH, followed by HPLC separation and analysis of the radioactivity incorporated into this derivatized GSH, the hydrolysis of the protective groups on the dipeptides prior to incorporation into GSH can be assumed.
21. Holleschau, A. M.; Rathbun, W. B.; Nagasawa, H. T. An HPLC radiotracer method for assessing the ability of L-cysteine prodrugs to maintain glutathione levels in the cultured rat lens. Curr. Eye Res., in press.
22. Rathbun, W. B. Glutathione in ocular tissues. Glutathione: chemical, biochemical, and medical aspects, Vol. III, Part B of the series Coenzymes and cofactors; Dolphin, D., Poulson, R., Avramovic, O., Eds.; Wiley: New York 1989; pp 467-510.
23. Epstein, D. L.; Kinoshita, J. H. The effect of diamide on lens glutathione and lens membrane function. Invest. Ophthal. 1970, 9, 629-638.
24. Epstein, D. L.; Kinoshita, J. H. Effect of methyl phenyldiazene-carboxylate (azoester) on lens membrane function. Exp. Eye Res. 1970, 10, 228-236.
25. Hazelton, G. A.; Lang, C. A. Glutathione contents of tissues in the aging mouse. Biochem. J. 1980, 188, 25-30.
26. Chen, T. S.; Richie, J. P.; Lang, C. A. Life span changes in acetaminophen detoxification in mice. Drug Metab. Disp. 1990, 18, 882-887.
27. (a) Martensson, J.; Steinherz, R.; Jain, A.; Meister, A. Glutathione ester prevents buthionine sulfoximine-induced cataract and lens epithelial cell damage. Proc. Natl. Acad. Sci. U.S.A. 1989, 86, 8727-8731.
28. (b) Maydani, M.; Martin, A.; Saatre, J.; Blumberg, J. B. The effect of glutathione (GSH) and GSH monoethyl ester (GSH-ME) on cataractogenesis in Emory mice and Sprague-Dawley rats. FASEB J. 1992, 6, 1906.
29. Chen, T. S., Richie, J. P.; Lang, C. A. Glutathione ester corrects the kidney glutathione and cysteine deficiencies in the aging mouse. Toxicologist 1990, 10, 320.
30. Crabb, T. A.; Hall, M. J.; Williams, R. O. Proton magnetic resonance studies of compounds with bridgehead nitrogen atomsXXVI. Configurational studies with derivatives of perhydrooxazolo[3,4-c]oxazole and the conformational analysis of perhydroimidazo[1,5-c]thiazole. Tetrahedron. 1973, 29, 3389-3398.
31. Nagasawa, H. T.; Elberling, J. A.; Shirota, F. N. Latentiated forms of the transport-inhibitory α-amino acid adamantanine. J. Pharm. Sci. 1980, 69, 1022-1025.
32. Nagasawa, H. T.; Goon, D. J. W.; Muldoon, W. P.; Zera, R. T. 2-Substituted thiazolidine-4(R)-carboxylic acids as prodrugs of L-cysteine. Protection of mice against acetaminophen hepatotoxicity. J. Med. Chem. 1984, 27, 591-596.