ISSN:
1573-904X
Keywords:
cytokine
;
rHuMGDF
;
PEGylation
;
diketopiperazine
;
stability
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract 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)rHuMGDF. 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 enhancedin-vitro shelf-life stability.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1011945704248
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