N-terminal site-specific mono-PEGylation of epidermal growth factor
SCIE
SCOPUS
- Title
- N-terminal site-specific mono-PEGylation of epidermal growth factor
- Authors
- Lee, H; Jang, IH; Ryu, SH; Park, TG
- Date Issued
- 2003-05
- Publisher
- KLUWER ACADEMIC/PLENUM PUBL
- Abstract
- Purpose. N-terminal site-specific mono-PEGylation of recombinant human epidermal growth factor (EGF) was accomplished using polyethyleneglycol ( PEG) derivatives (Mw = 2000 and 5000) through a reactive terminal aldehyde group. Methods. The site-specific PEG conjugation was conducted at a slightly acidic pH condition (pH 5.5). The mono-PEGylation was targeted to an alpha-amine group at the N-terminal end of EGF to minimize reduction of biologic activity. Tryptic digestion mapping and MALDI-TOF MS techniques were applied to show the occurrence of mono-PEGylation at the N-terminus of EGF. Results. The site-specific mono-PEGylated EGF, when compared with native EGF, fully retained its in vitro biologic activities such as cell proliferation and intracellular signal transduction. This revealed that although a synthetic polymer of a PEG was covalently conjugated to EGF, the internalized complex of PEGylated EGF-receptor within cells did not hamper the intracellular signal transduction events. The PEGylated EGF also exhibited a prolonged circulation in blood stream in vivo and markedly enhanced physical stability when incubated with tissue homogenate. Conclusion. N-terminally mono-PEGylated EGF shows increased physical stability while retaining its biologic activity.
- Keywords
- epidermal growth factor (EGF); poly(ethylene glycol) (PEG); site-specific PEGylation; biologic activity; RECEPTOR TYROSINE KINASES; POLYETHYLENE-GLYCOL; DIRECTED MUTAGENESIS; CELLS; ENDOCYTOSIS; EGF; IMMUNOGENICITY; MICROSPHERES; CONJUGATION; STABILITY
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/18566
- DOI
- 10.1023/A:1023402123119
- ISSN
- 0724-8741
- Article Type
- Article
- Citation
- PHARMACEUTICAL RESEARCH, vol. 20, no. 5, page. 818 - 825, 2003-05
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