Valine hydroperoxides, structure

Another derivatization approach is reduction of the hydroperoxide, followed by structural characterization of the corresponding alcohol, which is usually easier to handle. Thus, the structure of amino acid hydroperoxides can be characterized more easily if, after having ascertained the hydroperoxide nature of the compound, it is reduced to the alcohol with NaBH4. The structure of three valine hydroperoxides obtained on y-radiation of bovine serum albumin, a tripeptide (31) or valine (34) was elucidated after reduction, hydrolysis (if necessary), chromatographic separation, and application of the usual MS and NMR methods on the individual hydroxy derivatives of valine. ... 

F21. Fu, S., Hick, L. A., Sheil, M. M., and Dean, R. T., Structural identification of valine hydroperoxides and hydroxides on radical-damaged amino acid, peptide, and protein molecules. Free Radicals Biol. Med. 19, 281-292 (1995). 

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. 

As already mentioned, one of the products of action of hydroxyl radicals on proteins is protein hydroperoxides (G6). Valine and lysine residues are particu-larily susceptible to hydroperoxide formation. Reduction of hydroperoxides produces respective hydroxy derivatives of amino acids. Three valine hydroxides derived from hydroperoxides of this amino acid have been characterized structurally as p-hydroxyvaline [(2S)-2-amino-3-hydroxy-3-methyl-butanoic acid], (2S,3S)-y-hydroxyvaline [(2S,3S)-2-amino-3-hydroxymethyl-butanoic acid], and (2S,3R)-y -hydroxyvaline [(2S,3R)-2-amino-3-hydroxymethyl-butanoic acid (Fig. 12). They are suggested to be possible markers of protein peroxidation (F21). 

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