Large-scale biophysical evaluation of protein PEGylation effects: in vitro properties of 61 protein entities

Research output: Contribution to journalJournal articlepeer-review

Standard

Large-scale biophysical evaluation of protein PEGylation effects : in vitro properties of 61 protein entities. / Vernet, Erik; Popa, Gina; Pozdnyakova, Irina; Rasmussen, Jakob Ewald; Grohganz, Holger; Giehm, Lise; Jensen, Malene Hillerup; Wang, Huabing; Plesner, Bitten; Nielsen, Hanne Mørck; Jensen, Knud Jørgen; Berthelsen, Jens; Sundström, Michael; van de Weert, Marco.

In: Molecular Pharmaceutics, Vol. 13, No. 5, 2016, p. 1587-1598.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Vernet, E, Popa, G, Pozdnyakova, I, Rasmussen, JE, Grohganz, H, Giehm, L, Jensen, MH, Wang, H, Plesner, B, Nielsen, HM, Jensen, KJ, Berthelsen, J, Sundström, M & van de Weert, M 2016, 'Large-scale biophysical evaluation of protein PEGylation effects: in vitro properties of 61 protein entities', Molecular Pharmaceutics, vol. 13, no. 5, pp. 1587-1598. https://doi.org/10.1021/acs.molpharmaceut.6b00049

APA

Vernet, E., Popa, G., Pozdnyakova, I., Rasmussen, J. E., Grohganz, H., Giehm, L., Jensen, M. H., Wang, H., Plesner, B., Nielsen, H. M., Jensen, K. J., Berthelsen, J., Sundström, M., & van de Weert, M. (2016). Large-scale biophysical evaluation of protein PEGylation effects: in vitro properties of 61 protein entities. Molecular Pharmaceutics, 13(5), 1587-1598. https://doi.org/10.1021/acs.molpharmaceut.6b00049

Vancouver

Vernet E, Popa G, Pozdnyakova I, Rasmussen JE, Grohganz H, Giehm L et al. Large-scale biophysical evaluation of protein PEGylation effects: in vitro properties of 61 protein entities. Molecular Pharmaceutics. 2016;13(5):1587-1598. https://doi.org/10.1021/acs.molpharmaceut.6b00049

Author

Vernet, Erik ; Popa, Gina ; Pozdnyakova, Irina ; Rasmussen, Jakob Ewald ; Grohganz, Holger ; Giehm, Lise ; Jensen, Malene Hillerup ; Wang, Huabing ; Plesner, Bitten ; Nielsen, Hanne Mørck ; Jensen, Knud Jørgen ; Berthelsen, Jens ; Sundström, Michael ; van de Weert, Marco. / Large-scale biophysical evaluation of protein PEGylation effects : in vitro properties of 61 protein entities. In: Molecular Pharmaceutics. 2016 ; Vol. 13, No. 5. pp. 1587-1598.

Bibtex

@article{8719f99bf98240a8a57dfc92f26e994b,
title = "Large-scale biophysical evaluation of protein PEGylation effects: in vitro properties of 61 protein entities",
abstract = "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.",
author = "Erik Vernet and Gina Popa and Irina Pozdnyakova and Rasmussen, {Jakob Ewald} and Holger Grohganz and Lise Giehm and Jensen, {Malene Hillerup} and Huabing Wang and Bitten Plesner and Nielsen, {Hanne M{\o}rck} and Jensen, {Knud J{\o}rgen} and Jens Berthelsen and Michael Sundstr{\"o}m and {van de Weert}, Marco",
year = "2016",
doi = "10.1021/acs.molpharmaceut.6b00049",
language = "English",
volume = "13",
pages = "1587--1598",
journal = "Molecular Pharmaceutics",
issn = "1543-8384",
publisher = "American Chemical Society",
number = "5",

}

RIS

TY - JOUR

T1 - Large-scale biophysical evaluation of protein PEGylation effects

T2 - in vitro properties of 61 protein entities

AU - Vernet, Erik

AU - Popa, Gina

AU - Pozdnyakova, Irina

AU - Rasmussen, Jakob Ewald

AU - Grohganz, Holger

AU - Giehm, Lise

AU - Jensen, Malene Hillerup

AU - Wang, Huabing

AU - Plesner, Bitten

AU - Nielsen, Hanne Mørck

AU - Jensen, Knud Jørgen

AU - Berthelsen, Jens

AU - Sundström, Michael

AU - van de Weert, Marco

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

U2 - 10.1021/acs.molpharmaceut.6b00049

DO - 10.1021/acs.molpharmaceut.6b00049

M3 - Journal article

C2 - 27043713

VL - 13

SP - 1587

EP - 1598

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

SN - 1543-8384

IS - 5

ER -

ID: 161942022