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Site-Specific PEGylation of Recombinant Consensus Interferon Mutant Ⅱ |
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Abstract ecombinant interferon alpha (IFN-alpha) has been proven useful for treating a variety of human cancers and viral diseases. Because of its short circulating half-life IFN-alpha is administered to patients by daily or thrice weekly injection for optimal effectiveness. Recombinant consensus interferon mutant Ⅱ (IFN-Con-m2, IIFNm2) was a mutant from IFN-Con with a free cysteine residues at position 86.The protein could be modified with a 2 kDa-maleimide PEG and the mono-PEGylated proteins were purified by CM Sepharose Fast Flow column chromatography. Mono-PEGylated IIFNm2 could be separated from multi-PEGylated IIFNm2 and unmodified IIFNm2 by stepwise elution. After purification, the purity of mono-PEG-IIFNm2 was up to 98%, and the biological activity was more than 5.0×106IU/mg. The test of anti-trypsin digestion suggested that PEGylation could improve the ability of avoiding the trypsin digestion. Pharmacokinetic experiments in rats demonstrated that the circulating half-life of the PEGylated protein was up to 11.5-fold longer than that of IIFNm2. These data could demonstrate the utility of site-specific PEGylation for creating highly potent, long-acting IIFNm2.
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Received: 13 December 2007
Published: 25 April 2008
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