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.
Battersby
J E
JE
Genentech, Inc., South San Francisco, California.
Hancock
W S
WS
Canova-Davis
E
E
Oeswein
J
J
O'Connor
B
B
D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D054659:Diketopiperazines; D013006:Growth Hormone / Q000737:chemistry*; D006801:Humans; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification; D010449:Peptide Mapping; D010879:Piperazines; D011994:Recombinant Proteins / Q000737:chemistry; D014357:Trypsin
D054659:Diketopiperazines; D010446:Peptide Fragments; D010879:Piperazines; D011994:Recombinant Proteins; D013006:Growth Hormone; D014357:Trypsin