Amino acids linkage isomers

The iodoacetyl group of both isomers reacts with sulfhydryls under slightly alkaline conditions to yield stable thioether linkages (Figure 9.7). They do not react with unreduced disulfides in cystine residues or with oxidized glutathione (Gorman et al., 1987). The thioether bonds will be hydrolyzed under conditions necessary for complete protein hydrolysis prior to amino acid analysis. 

Because L-Xaa2-containing peptides have never been found in amphibian skin extracts, the epimerization mechanism probably involves a quantitative inversion of the chirality of the a-carbon of the amino acid residue, rather than a racemization, which would yield an equimolar mixture of L and D isomers [16,17]. Enzymes catalyzing the formation of D amino acids are so far known only in yeast [18]. From Bombina skin secretions Kreil et al. [19] recently purified a 52-kDa glycoprotein which catalyzes the reaction Ile-Ile-Gly to Ile-D-allo-Ile-Gly. The partial conversion of He to D-allo-Ile in peptide linkage proceeds without the addition of cofactors. 

There are two procedures used by chemists that imitate the natural pathway. In one, actual microorganisms are used in fermentation reactions that can directly produce some L-amino acids. In the other, enzymes are used to react with one enantiomer of a racemic pair. As you might guess, it is usually the L isomer that is eaten by the enzyme, because enzymes have evolved in an environment of L isomers. So it is usually the D isomers that are ignored by enzymes. In an extraordinarily clever procedure, this preference for natural, L, enantiomers can be used to achieve a kinetic resolution (Fig. 23.15). The mixture of enantiomers is first acetylated to create amide linkages. An enzyme, hog-kidney acylase, then hydrolyzes the amide linkages of only L-amino acids. So, treatment of the pair of acetylated amino acids leads to formation of the free L-amino acid. The acylat-ed D enantiomer is unaffected by the enzyme, which has evolved to react only with natural L-amino acids. The free L-amino acid can then easily be separated from the residual D acetylated material. 

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