1.Interferon alpha-2b modified with polyethylene glycol.
Yingxin WU ; Yanqin ZHAI ; Jiandu LEI ; Guanghui MA ; Zhiguo SU
Chinese Journal of Biotechnology 2008;24(9):1658-1663
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.
Animals
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Antiviral Agents
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chemistry
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pharmacokinetics
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Drug Stability
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Humans
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Interferon-alpha
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chemistry
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pharmacokinetics
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Polyethylene Glycols
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chemistry
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Rats
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Rats, Sprague-Dawley
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Recombinant Proteins