Model studies of competing hydrolysis and epimerization of some tetrapeptides of interest in amino acid racemization studies in geochronology

The processes of epimerization of individual peptide units in proteins and the concurrent cleavage of peptide bonds are modelled by heating some tetrapeptide and tetrapeptide derivatives to 148.5 °C in pH 6.8 phosphate buffer. An excess of D-proline was observed during the heating of L-prolyl-L-leucylglycylglycine. The D/L ratio of proline attains a maximum value of 2.1 after 90 minutes. The excess D-proline is attributed to the formation of a 2.3:1 mixture of diketopiperazines cyco-(D-prolyl-L-leucyl) and cyclo-(L-prolyl-L-leucyl). These two species account for most of the leucine and proline in the final mixture after the tetrapeptide is no longer detectable. Only small amounts of prolylleucine can be detected after 50 hours. It is suggested that the above tetrapeptide undergoes internal aminolysis. Leucine in the tetrapeptide glycyl-L-leucylglycylglycine racemizes three times faster than in L-prolyl-L-leucylglycylglycine. This demonstrates that an amino acid residue in a peptide chain does have an effect upon the rate of epimerization of a neighbouring peptide residue. A discussion of the geochemical implications of the results is included.