title: PEG-interferon conjugates: effects of length and structure of linker.
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.
authors: Centre for Applied Molecular Biology, Ministry of Science and Technology, Lahore, Pakistan.
authors: Muhammad Farooq
authors: MF
authors: Sabar
authors: Samra
authors: S
authors: Kausar
authors: Ahmad Usman
authors: AU
authors: Zafar
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002417:Cattle; D002460:Cell Line; D002626:Chemistry, Pharmaceutical; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004355:Drug Stability; D016898:Interferon-alpha / Q000138:chemical synthesis* / Q000494:pharmacology*; D015394:Molecular Structure; D008970:Molecular Weight; D011092:Polyethylene Glycols / Q000138:chemical synthesis* / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013678:Technology, Pharmaceutical / Q000379:methods; D018116:Vesiculovirus / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a