Related Experiment Videos
PEGylation prevents the N-terminal degradation of megakaryocyte growth and development factor
P I Guerra1, C Acklin, A A Kosky
1Department of Pharmaceutics, Amgen Inc., Thousand Oaks, California 91320, USA.
Purpose:
Determine the effect of PEGylation on in-vitro degradation for recombinant human Megakaryocyte Growth and Development Factor (rHuMGDF) in the neutral pH range.
Methods:
Degradation products were characterized by cation-exchange HPLC, N-terminal sequencing and mass spectrometry.
Results:
The main route of degradation was through non-enzymatic cyclization of the first two amino acids and subsequent cleavage to form a diketopiperazine and des(Ser, Pro)rHuMGDE This reaction was prevented by alkylation of the N-terminus by polyethylene glycol (PEG).
Conclusions:
PEGylation of proteins is commonly performed to achieve increased in-vivo circulation half-lives. For rHuMGDF, an additional advantage of PEGylation was enhanced in-vitro shelf-life stability.