Chemical stability and plasma-catalyzed dealkylation of peptidyl-alpha-hydroxyglycine derivatives--intermediates in peptide alpha-amidation.

The production of alpha-amidated peptides has recently been shown to occur via a two-step process with peptidyl-alpha-hydroxyglycine being an intermediate. In this study the chemical stability and plasma-catalyzed conversion of various peptidyl-alpha-hydroxyglycine derivatives to their parent amide product have been examined. This conversion was shown to be independent of pH in the range pH 1-5 and to be apparently specific base-catalyzed at pH 6-10. At pH 7.4 and 37 degrees C the half-lives of decomposition of the derivatives ranged from 5.8 to 13.3 h. In 80% human plasma solutions (pH 7.4) the half-lives decreased to 1.3-3.9 h, indicating the occurrence of an enzyme activity in plasma catalyzing the dealkylation of peptidyl-alpha-hydroxyglycine derivatives. The best substrate for the plasma catalytic activity was found to be N-benzyloxycarbonyl-L-alanyl-alpha-hydroxyglycine.