PEGylation Prevents the N-Terminal Degradation of Megakaryocyte Growth and Development Factor

PEGylation of proteins is commonly performed to achieve increased in-vivo circulation half-lives. For rHuMGDF, an additional advantage of PEGylation was enhancedin-vitro shelf-life stability.

Determine the effect of PEGylation on in-vitro degradation for recombinant human Megakaryocyte Growth and Development Factor (rHuMGDF) in the neutral pH range. Degradation products were characterized by cation-exchange HPLC, N-terminal sequencing and mass spectrometry. 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)rHuMGDF. This reaction was prevented by alkylation of the N-terminus by polyethylene glycol (PEG).

Leave a Reply