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Article Abstract
Di-branched (Y-shaped) polyethylene glycols (PEGs) are considered more effective than linear molecules to enhance the efficacy of the conjugated drug. In the present study interferon α-2a was conjugated with three different 40 KDa di-branched PEGs. The results of this study show that length and/or the structure of linker between PEG and the protein is also involved in the synthesis, in vitro biological activity and stability of the conjugate. Three conjugates i.e., mPEG2L-IFN, mPEG2P-IFN and mPEG(2)M-IFN yielded 25%, 24% and 17%, with bioactivities 2.8 x 10(6) IU/mg, 3.95 x 10(6) IU/mg and 6.7 x 10(6) IU/mg, respectively. The order of bioactivity stability is mPEG2L-IFN > mPEG2P-IFN > mPEG2M-IFN > IFN (native). We report that although lengthy linkers are more reactive in terms of conjugation, they have opposite effect on the in vitro bioactivity of the conjugate. PEGylation as a whole increases the stability of the conjugate, and linkers also add in stability.
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