Polymer selection impacts the pharmaceutical profile of site specifically conjugated Interferon-α2a

22 February 2022, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Conjugation of poly(ethylene glycol) (PEG) to biologics is a successful strategy to favorably impact the pharmacokinetics and efficacy of the resulting bioconjugate. We compare bioconjugates synthesized by strain-promoted azide-alkyne cycloaddition (SPAAC) using PEG and linear polyglycerol (LPG) of about 20 kDa or 40 kDa, respectively, with an azido functionalized human Interferon-α2a (IFN-α2a) mutant. Site specific PEGylation and LPGylation resulted in IFN-α2a bioconjugates with improved in vitro potency as compared to commercial Pegasys. LPGylated bioconjugates had faster disposition kinetics despite comparable hydrodynamic radii to their PEGylated analogues. Overall exposure of the PEGylated IFN-α2a with a 40 kDa polymer exceeded Pegasys which, in return, was comparable to the 40 kDa LPGylated conjugates. The study points to an expanded polymer design space by means of which the selected polymer class may result in different distribution of the studied bioconjugates.


genetic code expansion
poly(ethylene glycol)
analytical ultracentrifugation

Supplementary materials

Hauptstein et al supporting information Polymer selection impacts the pharmaceutical profile of site specifically conjugated Interferon alpha 2a
Supporting results include results of size exclusion chromatography, NMR of polymers, additional AUC results, full chromatograms of RP-HPLC analysis, SDS-PAGE of 20 and 40 kDa bioconjugate purifications, MALDI-TOF MS results, potency stimulation curves, additional DSF data, results of human plasma stability and FACS analysis of IFN-α2a stimulated murine bone marrow cells.


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