Site Directed Disulfide Pegylation of Interferon-Β-1B With Fork Peptide Linker Publisher Pubmed



Abbasi S^{1, 2} ; Farahani H³ ; Lanjanian H¹ ; Taheri M² ; Firoozpour L⁴ ; Davoodi J¹ ; Pirkalkhoran S⁵ ; Riazi G¹ ; Pooyan S^{1, 2}
Source: Bioconjugate Chemistry Published:2020

Abstract

The attachment of PEG to biopharmaceuticals has been applied for enhancement of bioavailability and improved stability. The PEG polymer is highly hydrated; thus effective attachment to inaccessible sites could be hindered. We have devised a scheme to address this issue by introducing a considerable distance between PEG and protein by addition of a linear peptide, appended to long chained reactive linkers. Second, the position of PEG conjugation directly affects biological activity. Accordingly, a disulfide bond could be considered as an ideal choice for site directed PEGylation; but reactivity of both thiol moieties to bridging reagent is critical for maintenance of protein structure. In our design, a forked structure with two arms provides essential flexibility to account for dissociation of reduced cysteines. An efficient yield for disulfide PEGylation of IFN-β1b was attained and specificity, biophysical characterization, biological activity, and pharmacokinetics were surveyed. Copyright © 2020 American Chemical Society.