Methionine sulphoxide

McLafferty rearrangement 133, 163 Meisenheimer complexes 699, 702 Metal-chelated intermediates 838 Metal-halogen exchange 781, 784 Methionine, oxidation of 852-855 Methionine sulphone 853 Methionine sulphoxide 851-869 reduction of 1063 residues of... 

Although single-electron-transfer (SET) processes would be expected to be important in reactions that use metals as reagents, this type of process has also been recognized in the reduction of carbonyl groups that involve 1,4-dihydronicotinamide derivatives . Recent work by Oae and coworkers" has shown that an SET process is operative in the reduction of dibenzothiophene S-oxide by l-benzyl-l,4-dihydronicotinamide when the reaction is catalyzed by metalloporphins. The reaction is outlined in equation (18), but the study gave results of much more mechanistic than synthetic value. This type of study is relevant to understanding biochemical mechanisms since it is known that methionine sulphoxide is reduced to methionine by NADPH when the reaction is catalyzed by an enzyme isolated from certain yeasts . 

Alpha-l-antiprotease (ai-AP) limits tissue damage arising from the actions of the leucocyte protease, elastase (Carrell and Travis, 1985), and there is much evidence available for the oxidative inactivation of this protein by oxygen-derived free-radical species and hypochlorous acid/hypochlorite anion (HOCl/OCP). The mechanism of this inactivation appears to involve the oxidation of a critical methionine residue (Met-358) to its corresponding sulphoxide and methionine sulphoxide has been detected in ai-AP samples isolated from the lungs of cigarette smokers (Carp et al., 1982) and rheumatoid synovial fluids (Wong and Travis, 1980). 

Exposure of the amino acid methionine to H2O2 or an OH radical flux generates methionine sulphoxide as a... 

Figure 1.5 High-field (aliphatic) regions of 400 MHz H Hahn spin-echo NMR spectra of (a) E-199 culture medium (b) as (a) but following a 2 h incubation with neutrophils at 37°C (c) as (b) but incubated in the presence of 1.00 x 10 mol/dm phorbol 12-myrlstate 13-acetate (PMA). For abbreviations, see Fig. 1.2 with Met, methionine-S-Ctl3 group resonance MetSO, methionine sulphoxide-SO-CHs group resonance. The 2.245 p.p.m. singlet detectable in spectrum (c) arises from the -CH3 groups of acetone, the solvent in which PMA was...

Amino-4-(methylsulphoxyl)butyric acid see methionine sulphoxide. 

S-Methyl-L-methionine chloride [1115-84-0] M 199.5, [a]Q +33 (0.2M HCl). Likely impurities are methionine, methionine sulphoxide and methionine sulphone. Crystd from water by adding a large excess of EtOH. Stored in a cool, dry place, protected from light. 

Pulmonary emphysema is associated with cigarette smoking in normal individuals, as well as with ajAT deficiency. In smokers, though absolute levels of aiAT are normal, elastase inhibitory activity is depressed [93]. This is due to the oxidation of a critical, reactive centre, methionine residue (met 358) to methionine sulphoxide [94], Likewise, a large proportion of aiAT is also inactivated in the rheumatoid joint cavity [95,96], even when synovial fluid samples are analysed immediately after aspiration [97]. Again,... 

Abbreviations used in tables include Ada = 1-adamantyl boro-AA-OH = boronic acid analogue of specified amino acid (aa) Cbz = benzyloxycarbonyl CMK = chloromethylketone EIM = enzyme inhibitor of monocytes -NA = p-nitroanilide ND = not determined NR = not reactive MeO-Suc = methoxy succinoyl Met(O) = methionine sulphoxide Pic = picolinyl PPE = porcine pancreatic elastase SLPI = secretory leukocyte proteinase inhibitor TFMK = trifluoromethylketone Z = benzyloxycarbonyl. 

The side-chain of methionine may be S-alkylated (see Table 1.3) or oxidised at S to give methionine sulphoxide. 

Previously, we have examined the formation of amino acid hydroperoxides following exposure to different radical species [100]. We observed that valine was most easily oxidised, but leucine and lysine are also prone to this modification in free solution. Scheme 12 illustrates the mechanism for formation of valine hydroperoxide. However, tertiary structure becomes an important predictor in proteins, where the hydrophobic residues are protected from bulk aqueous radicals, and lysine hydroperoxides are most readily oxidised. Hydroperoxide yield is poor from Fenton-derived oxidants as they are rapidly broken down in the presence of metal ions [101]. Like methionine sulphoxide, hydroperoxides are also subject to repair, in this case via glutathione peroxidase. They can also be effectively reduced to hydroxides, a reaction supported by the addition of hydroxyl radical in the presence of oxygen. Extensive characterisation of the three isomeric forms of valine and leucine hydroxides has been undertaken by Fu et al. [102,103], and therefore will not be discussed further here. 

A recent study has described the inhibition of tyrosine nitration but not oxidation by tryptophan and tryptamine, indicating that nitration of the indole ring proceeds more favourably than nitration of the phenoxyl ring [118]. Methionine oxidation can be elicited by peroxynitrite and proceeds via two-step single electron reduction reactions yielding methionine sulphoxide as described previously [119]. 

Reducing equivalents from a ven thioredoxin can be donated to a variety of reductase enzymes. They are not specific for the nucleotide reductase or for enzymes from the same organism. Reduced yeast thioredoxin will serve as reductant for methionine sulphoxide reductase, sulphate reductase and the E. coli nucleoside diphosphate reductase. Heat-stable protein cofactors are known to be involved in each of these systems. 

Methionine sulphoxide-containing peptides invariably elute earlier than the corresponding unoxidized materiaL... 

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