L-Methionine sulfoxide

FIGURE 7. The enzymatic reduction of N-acetyl-L-methionine sulfoxide. 

BM Iselin. Derivatives of L-methionine sulfoxide and their use in peptide syntheses. Helv ( him Ada 44, 61, 1961. 

The (5 -configuration at the sulfur atom was assigned (49) to the naturally occurring L-methionine sulfoxide 28 based on the results of its thermal decarboxylation, leading to the formation of the dextrorotatory enantiomer of 3-methylsulfinylpropylamine 187 of known absolute (iS)-configuration at chiral sulfur. 

Metabolic Transit of U-14C-L-Methionine Sulfoxide. U-14C-L-methionine sulfoxide was prepared according to the method of Lepp and Dunn (67) and its metabolic transit on rats was compared with that of free U-14C-L-methionine of the same specific activity (28). 

Table V. Metabolism of 14C-L-Methionine and 14C-L-Methionine Sulfoxide in Ratsa...

Figure 3. Kinetics of 14CG2 expiration in rats after oral ingestion of U-14C-lu-methionine and U-14C-L,-methionine sulfoxide (each curve corresponds to one...

I. Iwami, Y. Higashiyama, F. Ibuki, Reevaluation of L-methionine sulfoxide bioavailability and a difference between its epimers in normal young-rats, Nutr. Res., 12 (1992), 1155-1166. 

Isolation and identification of y-L-glutamyl-L-methionine sulfoxide from green... 

Pitha, J., Szente, L., and Greenberg, J. Poly-L-methionine sulfoxide a biologically inert analogue of dimethyl sulfoxide with solubilizing potency. J. Pharm. Sci. 72, 665-668 (1983). 

S-Methyl-L-methionine chloride (Vitamin U) [1115-84-0] M 199.5, [a]p +33 (0.2M pK[ 1.9, pKj 7.9. Likely impurities are methionine, methionine sulfoxide and methionine sulfone. from water by adding a large excess of EtOH. Stored in a cool, dry place, protected from light. 

ACTH, adrenocorticotrophic hormone Met, methionine Met(O), methionine sulfoxide DTT, dithiothreitol L7, L12, Escherichia coli ribosomal proteins Met(0)-L12, L12 containing Met(O) residues a-l-PI, a-1-proteinase inhibitor Met(0)-a-l-PI, a-l-PI... 

Methionine sulfoxide chemistry and biochemistry TABLE 6. Requirements for the reduction of Met(0)-a-l-PI ... 

Figure 4.11 Chromatograms of (1) de s AI a1 (S58-S1 °5) S er1125 IL-2, (2) desAla1 (SH58, SH105)Ser125 IL-2, and (3) mixture of all components. Peaks labeled A have methionine sulfoxide at position 104, and peaks labeled B have unoxidized methionine at position 104. Separations were performed using a gradient of 41-60% acetonitrile-water (0.1% TFA) in 60 min at 0.5 ml/min. (Reproduced from M.G. Kunitani, D.J. Johnson, and L.R. Snyder, J. Chromatogr., 371 313 [1986]. With permission from Elsevier Science.)...

This enzyme [EC 1.8.4.5], also known as methionine S-oxide reductase, catalyzes the reaction of L-methionine with oxidized thioredoxin to produce L-methionine S-oxide and reduced thioredoxin. Dithiothreitol can substitute for reduced thioredoxin in the reverse reaction. In addition, other methyl sulfoxides can replace methionine sulfoxide in the reverse reaction. 

The sulfur analog of the selenoxide pyrolysis is also known. In this sulfoxide pyrolysis the C-S bond is broken. The C-S bond is stronger than the C-Se bond and this explains why sulfoxides must typically be pyrolyzed at 200 °C to achieve elimination. Figure 4.13 shows the transformation of protected L-methionine into the corresponding sulfoxide, which then undergoes sulfoxide pyrolysis. This two-step sequence provides an elegant access to the nonnatural amino acid L-vinyl glycine. 

Labeling of Sulfur Compounds in Tissue with S35. The German cockroach, Blattella germanica (L.), selected for this study because of the large amounts of free methionine sulfoxide observed in previous investigations (5), was reared on a fortified dog biscuit diet (5) at 24° C. Full-grown nymphs were used without attempting to separate the sexes. 

The repair of oxidative damage may be incomplete. Only reduction of the d-diastereomer of calmodulin-bound methionine sulfoxide (L-Met-D-SO) by methionine sulfoxide reductase was demonstrated, while in the cells both d- and l-steoreoisomers are formed. Such incomplete, diastereoselective repair by methionine sulfoxide reductase contributes to the accumulation of methionine sulfoxide residues during oxidative stress and aging in vivo (S24). 

All these enzymes have similar specificity and require the L-cysteine sulfoxide portion of the molecule. S-alkyl cysteines are not substrates 18, 24, 27, 39) neither are sulfoxides of N-substituted L-cysteine, / -di-methyl-L-cysteine, y8-thiopropionic acid 18), D-cysteine 19), and dl-methionine 18, 24, 39), nor do the enzymes act on L-cysteine itself 24, 27, 39), cysteic acid, cysteinesulfinic acid 24, 27), or cycloalliin 24, 39). There may be some action on S-ethylcysteine sulfone (42). 

In order to prevent S-alkylation in the repetitive acid-cleavage steps required in a multistep peptide synthesis, the protection of methionine residues as sulfoxides was proposed by Iselin.f This approach has since been widely used for peptide synthesis in solution and on solid supports.Generally, oxidation of L-methionine yields a mixture of S- and R-sulf-oxides and, depending on the conditions used, even a mixture of the related sulfone. Thereby, at least by oxidation with hydrogen peroxide the R-sulfoxide is formed in a preferred manner (80%), whereas oxidation of L-methionine by tetrachloroauric(III) acid has been reported to produce stereospecifically the 5-sulfoxide diastereoisomer. Isomeric pure Met(O) derivatives are obtained by isolation of the isomers from the 5,/ -sulfoxide mixture, taking advantage of the differences in solubility of the picrate salts.0 ... 

Scheme 2 Reduction of Methionine Sulfoxide with Sulfur Trioxide/Thiol in Organic Solventsl l...

The place of L-glutamine in hyaluronate synthesis is shown by experiments with methionine sulfoxide. Since methionine sulfoxide (2-amino-4-methylsulfinylbutyric acid) inhibits L-glutamine formation the addition of the sulfoxide to a culture of hemolytic streptococci inhibits hexosamine synthesis and, consequently, hyaluronate formation. This inhibition can take place at concentrations of methionine sulfoxide which are low enough not to inhibit hyaluronate synthesis with L-glutamine. ... 

Amino acid substitutions have been examined in every position of dermorphin (see Ref 663 for a review). An alanine scan of the peptide indicated that substitutions in positions 4, 6, and 7 are well tolerated, whereas substitution particularly in positions 1 or 2, but also in positions 3 or 5, results in large decreases in potency in the GPI (877). A o-amino acid in position 2 is important for activity, and the L-Ala peptide is virtually inactive (<0.1% the potency of dermorphin). Tetrapeptide analogs containing D-methionine sulfoxide in position 2 are also potent p-selective agonists (878). 

Etienne, F., Resnick, L., Sagher, D., Brot, N., and Weissbach, H. (2003) Reduction of sulindac to its active metabolite, sulindac sulfide assay and role of the methionine sulfoxide reductase system. Biochem. Biophys. Res. Commun. 312, 1005-1010. 

This paper (S4) compares the two silylating reagents bis (trimethyl-silyl) acetamide (BSA), first described by Klebe et ad. (K6), and bis-(trimethylsilyl) trifluoroacetamide (BSTFA), for the preparation of volatile trimethylsilyl (TMS) derivatives of 12 sulfur-containing amino acids. BSTFA was recommended as the reagent of choice for taurine, cysteic acid, homocystine, djenkolic acid, ethionine, methionine sulfone, L-2-thiolhistidine, cysteine, and cystine. For S-methyl-L-cysteine, methionine sulfoxide, and methionine, BSA was used as silylating reagent. 

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