PEG-interferon conjugates: Effects of length and structure of linker

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 mpeg2m-ifn yielded 25%, 24% and 17%, with bioactivities 2.8 x 106 iu/mg, 3.95 x 106 iu/mg and 6.7 x 106 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.