Glutamyl derivatives

The interplay of kidney-selective transport and/or kidney-selective activation is well illustrated by the prodrug y-glutamyl sulfamethoxazole (6.24, R=H) and some A-acyl-y-glutamyl derivatives (6.24, R=acyl) [41], y-Glu-sulfamethoxazole, indeed, released sulfamethoxazole at high rates in kidney homogenates, whereas other organs showed low or negligible activity. Its... 

M. Orlowski, H. Mizoguchi, S. Wilk, W-Acyl-y-glutamyl Derivatives of Sulfamethoxazole as Models of Kidney-Selective Prodrugs , J. Pharmacol. Exp. Ther. 1980,212,167 -172. 

Orlowski, M., H. Mizoguchi, andS. Wilk. 197SN-Acyl-y-glutamyl derivatives of sulfamethoxazole as models of kidney-selective prodrugsl. Pharmacol. Exp. The212 167-172. 

Amino acid 78 and its y-glutamyl derivative are other components of the major pool of seleno compounds in accumulator plants, while selenomethionine (79) is the major compound in microorganisms like yeast, which is not specialized in selenium utilization. Se-Methylselenocysteine 5e-oxide (80), which is found in marine algae, tends to spontaneously decompose with the formation of pyruvate and ammonia via aminoacrylic acid and methaneselenic acid (81). The latter reacts with sulfhydryls or selenols to selenodisulfldes and diselenides. 

Block, E., Birringer, M., Jiang, W., Nakahodo, T., Thompson, H. J., et al. Allium chemistry synthesis, natural occurence, biological activity, and chemistry of Se-alk(en)ylselenocysteines and their y-glutamyl derivatives and oxidation products. J Agric Food Chem 2001, 49, 458 470. Das, A., Desai, D., Pittman, B., Amin, S., El-Bayoumy, K. Comparison of the chemopreventive efficacies of l,4-phenylenebis(methylene)selenocyanate and selenium-enriched yeast on 4-(methylnitrosamino)-l-(3-pyridyl)-l-butanone induced lung tumorigenesis in A/J mouse. Nutr Cancer 2003, 46, 179-185. 

Orihara, T. and Furuya, T. 1990. Production of theanine and other y-glutamyl derivatives by Camellia sinensis cultured cells. Plant Cell. Rep. 9 65-68. 

Further examples of the ability to elaborate the terminal amino group in (VIII.296) and (VIII.297) were provided [368] in the reaction of these compounds with ethyl isocyanotoacetate, which gave the glycyl derivatives (VIII.301) (45%) and (VIII.302) (61%), and with diethyl 2-isoeyanatoglutar-ate, whieh gave the glutamyl derivatives (VIII.303) (72%) and (VIII.304)... 

Glutathione, y-glutamyl derivatives, and (3-lyase substrates have been investigated as renal-specific prodrugs based on the presence of certain transporters such as plasma membrane transport systems for glutathione [28] and cysteine [29] conjugates and/or enzymes such as y-glutamyltrans-ferase (EC 2.3.2.2), dipeptidase, and p-lyase (EC4.4.1.13). 

Ester Formation. Esters of iV-protected amino acids are prepared in high yield with EDC and 4-Dimethylaminopyridine (eq6). DMAP causes extensive racemization if not used in a catalytic amount. However, when esterifying the a-carboxyl of /3- and y-benzyl esters of aspartyl and glutamyl derivatives, extensive racemization was observed even with DMAP present in catalytic amounts. It is postulated that the side-chain esters contribute in some fashion to the lability of the cr-H. 

During germination of kidney beans, in which 5-methylcysteine is present mainly in the form of the y-glutamyl derivative, there is a net loss of over 70% of the total -y-glutamyl-5-methylcysteine. Since no increase in acidic peptides equivalent to the net loss of y-glutamyl-5-methylcysteine could be detected, it was concluded that hydrolysis rather than transpeptidation had occurred, and it was suggested (Thompson et al., 1962) that y-... 

But a carrier can be fairly simple, as in the transport of amino acids from urine into proximal renal tubule cells. These convert the amino acid to its y-glutamyl derivative by the action ofglutamyltransferase and glutathione. Once inside the cell, the glutamyl group is excised and reconverted to glutathione (Meister and Tate, 1976). 

Contents B. FRASER-REID and R. C. ANDERSON, Carbohydrate Derivatives in the Asymmetric Synthesis of Natural Products — H. JONES and G. H. RASMUSSON, Recent Advances in the Biology and Chemistry of Vitamin D — S. LIAAEN-JENSEN, Stereochemistry of Naturally Occurring Carotenoids — T. KASAI and P. O. LARSEN, Chemistry and Biochemistry of y -Glutamyl Derivatives from Plants Including Mushrooms (Basidiomycetes) - Author Index - Subject Index. 

In addition to these ubiquitous amino acids, an additional 700 amino acids that are not involved in primary metabolism have been reported. About 300 of these are found in plants (Hunt, 1991). Most nonprotein amino acids occur free, as their 4-glutamyl (or y-glutamyl) derivatives, or linked to carbohydrate moieties. There are two main types of nonprotein amino acids. A number of nonprotein amino acids are similar to primary amino acids others are unrelated to any of these. Members of the first group may arise in three principal ways. Some nonprotein amino acids arise by simple structural modifications of protein amino acids others arise by modification of the pathways leading to protein amino acids a third group arises by novel routes. 

Nonprotein amino acids usually occur free in plants, or as their 4-glutamyl derivatives. These amino acids generally are extracted with ethanol or with alcohol-water mixtures (Rosenthal, 1982, 1991). Most amino acids can be detected by the characteristic reaction with ninhydrin, which produces blue to purple colored chromophores (Rosenthal, 1991). Most of the early work with nonprotein amino acids was done using paper-chromatographic and thin-layer techniques... 

Among the amino acids from Lathyrus are 2,4-diamino-butyric acid (56) (a neurologically active factor) see above), A -oxalyl-2,3-diaminopropionic acid (57) (a potent neurotoxin), 3-cyanoalanine (58) (a neurotoxin), and the 4-gluta-myl derivative of 3-cyanoalanine. The decarboxylation product of 3-cyanoalanine, 3-aminopropionitrile (59), and its 4-glutamyl derivative induce many of the osteolathyritic skeletal abnormalities (Rosenthal, 1991) (Fig. 13.13). 

Cyanoalanine 0-cyanoalanine) (58) is the only nonprotein amino acid with a cyano group. Normally, cyanide in plants is incorporated into asparagine, but in Vida sativa, the 4-glutamyl derivative of 3-cyanoalanine is produced. The most efficient amino acid precursors for 3-cyanoalanine are serine (11) and cysteine (12) (Fig. 13.15) (Rosenthal, 1982). 

Consumption of seeds of the genus Lathyrus (Fabaceae) by man and his domestic animals produces a syndrome called lathyrism. Different amino acids produce the two forms of this malady neurolathyrism and osteolathyrism. 3-Aminopropionitrile 0-aminopropionitrile) (59) is the active osteolathyritic factor in Lathyrus species. Several factors are responsible for neurolathyrism. 3-Cyanoalanine (58), its 4-glutamyl derivative, 2,4-diaminobutyric acid (56), and the N-oxalyl derivative of 2,3-diaminopropionic (a,3-diamino-propionic) acid (57) are all known to be involved. These compounds are found primarily in plants of the genus iMth-yrus. 3-Cyanoalanine (58) and its 4-glutamyl derivative are also common in Vida species. Several related series of compounds are found in other members of the Fabaceae. 

Many nonprotein amino acids occur in plants as their 7-glutamyl derivatives and are discussed in Chapter 13. 

Chemistry and Biochemistry of y-Glutamyl Derivatives from Plants Including Mushrooms (Basidiomycetes)... 

IV. Chemical, Spectroscopic, and Analytical Properties of y-Glutamyl Derivatives 217... 

Degradation and General Chemical Properties of y-Glutamyl Derivatives. . 224... 

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