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Appl Microbiol Biotechnol ; 101(5): 1975-1987, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27833991

RESUMO

Recombinant interferon-ß1b (IFN-ß1b) is an effective remedy against multiple sclerosis and other diseases. However, use of small polypeptide (molecular weight is around 18.5 kDa) is limited due to poor solubility, stability, and short half-life in systemic circulation. To solve this problem, we constructed two variants of PASylated IFN-ß1b, with PAS sequence at C- or N-terminus of IFN-ß1b. The PAS-modified proteins demonstrated 4-fold increase in hydrodynamic volume of the molecule combined with 2-fold increase of in vitro biological activity, as well as advanced stability and solubility of the protein in solution as opposed to unmodified IFN-ß1b. Our results demonstrate that PASylation has a positive impact on stability, solubility, and functional activity of IFN-ß1b and potentially might improve pharmacokinetic properties of the molecule as a therapeutic agent.


Assuntos
Fatores Imunológicos/metabolismo , Interferon beta-1b/genética , Interferon beta-1b/metabolismo , Processamento de Proteína Pós-Traducional , Proteínas Recombinantes/metabolismo , Meia-Vida , Humanos , Fatores Imunológicos/genética , Fatores Imunológicos/uso terapêutico , Interferon beta-1b/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Estabilidade Proteica , Proteínas Recombinantes/genética , Proteínas Recombinantes/uso terapêutico , Solubilidade
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