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Large-Scale Biophysical Evaluation of Protein PEGylation Effects: In Vitro Properties of 61 Protein Entities.
Vernet, Erik; Popa, Gina; Pozdnyakova, Irina; Rasmussen, Jakob E; Grohganz, Holger; Giehm, Lise; Jensen, Malene H; Wang, Huabing; Plesner, Bitten; Nielsen, Hanne M; Jensen, Knud J; Berthelsen, Jens; Sundström, Michael; van de Weert, Marco.
Afiliación
  • Vernet E; Novo Nordisk A/S , 2880 Bagsværd, Denmark.
  • Popa G; The Novo Nordisk Foundation Center for Protein Research (NNF CPR), Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen, Denmark.
  • Pozdnyakova I; The Novo Nordisk Foundation Center for Protein Research (NNF CPR), Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen, Denmark.
  • Rasmussen JE; The Novo Nordisk Foundation Center for Protein Research (NNF CPR), Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen, Denmark.
  • Grohganz H; Department of Chemistry, Faculty of Science, University of Copenhagen , Copenhagen, Denmark.
  • Giehm L; Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen, Denmark.
  • Jensen MH; Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen, Denmark.
  • Wang H; Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen, Denmark.
  • Plesner B; Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen, Denmark.
  • Nielsen HM; Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen, Denmark.
  • Jensen KJ; Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen, Denmark.
  • Berthelsen J; Department of Chemistry, Faculty of Science, University of Copenhagen , Copenhagen, Denmark.
  • Sundström M; Costerton Biofilm center, Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen, Denmark.
  • van de Weert M; The Novo Nordisk Foundation Center for Protein Research (NNF CPR), Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen, Denmark.
Mol Pharm ; 13(5): 1587-98, 2016 05 02.
Article en En | MEDLINE | ID: mdl-27043713
PEGylation is the most widely used method to chemically modify protein biopharmaceuticals, but surprisingly limited public data is available on the biophysical effects of protein PEGylation. Here we report the first large-scale study, with site-specific mono-PEGylation of 15 different proteins and characterization of 61 entities in total using a common set of analytical methods. Predictions of molecular size were typically accurate in comparison with actual size determined by size-exclusion chromatography (SEC) or dynamic light scattering (DLS). In contrast, there was no universal trend regarding the effect of PEGylation on the thermal stability of a protein based on data generated by circular dichroism (CD), differential scanning calorimetry (DSC), or differential scanning fluorimetry (DSF). In addition, DSF was validated as a fast and inexpensive screening method for thermal unfolding studies of PEGylated proteins. Multivariate data analysis revealed clear trends in biophysical properties upon PEGylation for a subset of proteins, although no universal trends were found. Taken together, these findings are important in the consideration of biophysical methods and evaluation of second-generation biopharmaceutical drug candidates.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polietilenglicoles / Proteínas Tipo de estudio: Prognostic_studies Idioma: En Revista: Mol Pharm Asunto de la revista: BIOLOGIA MOLECULAR / FARMACIA / FARMACOLOGIA Año: 2016 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polietilenglicoles / Proteínas Tipo de estudio: Prognostic_studies Idioma: En Revista: Mol Pharm Asunto de la revista: BIOLOGIA MOLECULAR / FARMACIA / FARMACOLOGIA Año: 2016 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Estados Unidos