Interferon alpha-2b modified with polyethylene glycol.
- Author:
Yingxin WU
1
;
Yanqin ZHAI
;
Jiandu LEI
;
Guanghui MA
;
Zhiguo SU
Author Information
1. National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100080, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Antiviral Agents;
chemistry;
pharmacokinetics;
Drug Stability;
Humans;
Interferon-alpha;
chemistry;
pharmacokinetics;
Polyethylene Glycols;
chemistry;
Rats;
Rats, Sprague-Dawley;
Recombinant Proteins
- From:
Chinese Journal of Biotechnology
2008;24(9):1658-1663
- CountryChina
- Language:Chinese
-
Abstract:
In order to obtain a more stable PEGylated interferon alpha-2b, and prolong its half life, interferon alpha-2b (IFN alpha-2b) was modified with monomethoxy polyethylene glycol propionaldehyde (mPEG-ALD) 20000. It was found that the optimized reaction condition for the maximum bioactivity and highest PEGylation degree of the mono PEGylated interferon alpha-2b was as follows: in 20 mmol/L, pH 6.5, citric acid and sodium dihydrogen phosphate buffer, the concentration of IFN alpha-2b was 4 mg/mL, and the molar ratio of PEG/IFN alpha-2b was 8:1, and the reaction time was 20 h at 4 degrees C. Under the optimized reaction condition, the mono PEGylation degree reached to 55%. Ion exchange chromatography was used to separate and purify mono PEGylated interferon alpha-2b from the reaction mixture. The purity of mono PEGylated interferon alpha-2b was higher than 97% characterized by HPLC. The bioactivity of the mono PEGylated interferon alpha-2b was 13.4% of the native IFN alpha-2b, while its half life in SD rat is much longer than the native IFN alpha-2b. The mono PEGylated interferon alpha-2b is also stable in aqueous.
