Site Directed Disulfide PEGylation of Interferon-ß-1b with Fork Peptide Linker.
Bioconjug Chem
; 31(3): 708-720, 2020 03 18.
Article
em En
| MEDLINE
| ID: mdl-31951391
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-ß1b was attained and specificity, biophysical characterization, biological activity, and pharmacokinetics were surveyed.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Polietilenoglicóis
/
Dissulfetos
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Interferon beta-1b
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article