Diketopiperazine formation and N-terminal degradation in recombinant human growth hormone

A new degradation process has been identified that occurs in recombinant DNA-derived human growth hormone. Non-enzymatic cyclization of the first two amino acids from the N-terminus and subsequent cleavage results in the formation of a diketopiperazine and a truncated variant of rhGH. The truncated protein was separated using hydrophobic interaction chromatography and identified as desPhe¹Pro²-rhGH using N-terminal sequence analysis, tryptic mapping, and mass spectrometry.