Preferential interactions and the effect of protein PEGylation

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Preferential interactions and the effect of protein PEGylation. / Holm, Louise Stenstrup; Thulstrup, Peter Waaben; Kasimova, Marina Robertovna; van de Weert, Marco.

I: PLOS ONE, Bind 10, Nr. 7, e0133584, 2015.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Holm, LS, Thulstrup, PW, Kasimova, MR & van de Weert, M 2015, 'Preferential interactions and the effect of protein PEGylation', PLOS ONE, bind 10, nr. 7, e0133584. https://doi.org/10.1371/journal.pone.0133584

APA

Holm, L. S., Thulstrup, P. W., Kasimova, M. R., & van de Weert, M. (2015). Preferential interactions and the effect of protein PEGylation. PLOS ONE, 10(7), [e0133584]. https://doi.org/10.1371/journal.pone.0133584

Vancouver

Holm LS, Thulstrup PW, Kasimova MR, van de Weert M. Preferential interactions and the effect of protein PEGylation. PLOS ONE. 2015;10(7). e0133584. https://doi.org/10.1371/journal.pone.0133584

Author

Holm, Louise Stenstrup ; Thulstrup, Peter Waaben ; Kasimova, Marina Robertovna ; van de Weert, Marco. / Preferential interactions and the effect of protein PEGylation. I: PLOS ONE. 2015 ; Bind 10, Nr. 7.

Bibtex

@article{edcd0e0bb95b4fa1a651fa3ae9ef657f,
title = "Preferential interactions and the effect of protein PEGylation",
abstract = "BACKGROUND: PEGylation is a strategy used by the pharmaceutical industry to prolong systemic circulation of protein drugs, whereas formulation excipients are used for stabilization of proteins during storage. Here we investigate the role of PEGylation in protein stabilization by formulation excipients that preferentially interact with the protein.METHODOLOGY/PRINCIPAL FINDINGS: The model protein hen egg white lysozyme was doubly PEGylated on two lysines with 5 kDa linear PEGs (mPEG-succinimidyl valerate, MW 5000) and studied in the absence and presence of preferentially excluded sucrose and preferentially bound guanine hydrochloride. Structural characterization by far- and near-UV circular dichroism spectroscopy was supplemented by investigation of protein thermal stability with the use of differential scanning calorimetry, far and near-UV circular dichroism and fluorescence spectroscopy. It was found that PEGylated lysozyme was stabilized by the preferentially excluded excipient and destabilized by the preferentially bound excipient in a similar manner as lysozyme. However, compared to lysozyme in all cases the melting transition was lower by up to a few degrees and the calorimetric melting enthalpy was decreased to half the value for PEGylated lysozyme. The ratio between calorimetric and van't Hoff enthalpy suggests that our PEGylated lysozyme is a dimer.CONCLUSION/SIGNIFICANCE: The PEGylated model protein displayed similar stability responses to the addition of preferentially active excipients. This suggests that formulation principles using preferentially interacting excipients are similar for PEGylated and non-PEGylated proteins.",
author = "Holm, {Louise Stenstrup} and Thulstrup, {Peter Waaben} and Kasimova, {Marina Robertovna} and {van de Weert}, Marco",
year = "2015",
doi = "10.1371/journal.pone.0133584",
language = "English",
volume = "10",
journal = "P L o S One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "7",

}

RIS

TY - JOUR

T1 - Preferential interactions and the effect of protein PEGylation

AU - Holm, Louise Stenstrup

AU - Thulstrup, Peter Waaben

AU - Kasimova, Marina Robertovna

AU - van de Weert, Marco

PY - 2015

Y1 - 2015

N2 - BACKGROUND: PEGylation is a strategy used by the pharmaceutical industry to prolong systemic circulation of protein drugs, whereas formulation excipients are used for stabilization of proteins during storage. Here we investigate the role of PEGylation in protein stabilization by formulation excipients that preferentially interact with the protein.METHODOLOGY/PRINCIPAL FINDINGS: The model protein hen egg white lysozyme was doubly PEGylated on two lysines with 5 kDa linear PEGs (mPEG-succinimidyl valerate, MW 5000) and studied in the absence and presence of preferentially excluded sucrose and preferentially bound guanine hydrochloride. Structural characterization by far- and near-UV circular dichroism spectroscopy was supplemented by investigation of protein thermal stability with the use of differential scanning calorimetry, far and near-UV circular dichroism and fluorescence spectroscopy. It was found that PEGylated lysozyme was stabilized by the preferentially excluded excipient and destabilized by the preferentially bound excipient in a similar manner as lysozyme. However, compared to lysozyme in all cases the melting transition was lower by up to a few degrees and the calorimetric melting enthalpy was decreased to half the value for PEGylated lysozyme. The ratio between calorimetric and van't Hoff enthalpy suggests that our PEGylated lysozyme is a dimer.CONCLUSION/SIGNIFICANCE: The PEGylated model protein displayed similar stability responses to the addition of preferentially active excipients. This suggests that formulation principles using preferentially interacting excipients are similar for PEGylated and non-PEGylated proteins.

AB - BACKGROUND: PEGylation is a strategy used by the pharmaceutical industry to prolong systemic circulation of protein drugs, whereas formulation excipients are used for stabilization of proteins during storage. Here we investigate the role of PEGylation in protein stabilization by formulation excipients that preferentially interact with the protein.METHODOLOGY/PRINCIPAL FINDINGS: The model protein hen egg white lysozyme was doubly PEGylated on two lysines with 5 kDa linear PEGs (mPEG-succinimidyl valerate, MW 5000) and studied in the absence and presence of preferentially excluded sucrose and preferentially bound guanine hydrochloride. Structural characterization by far- and near-UV circular dichroism spectroscopy was supplemented by investigation of protein thermal stability with the use of differential scanning calorimetry, far and near-UV circular dichroism and fluorescence spectroscopy. It was found that PEGylated lysozyme was stabilized by the preferentially excluded excipient and destabilized by the preferentially bound excipient in a similar manner as lysozyme. However, compared to lysozyme in all cases the melting transition was lower by up to a few degrees and the calorimetric melting enthalpy was decreased to half the value for PEGylated lysozyme. The ratio between calorimetric and van't Hoff enthalpy suggests that our PEGylated lysozyme is a dimer.CONCLUSION/SIGNIFICANCE: The PEGylated model protein displayed similar stability responses to the addition of preferentially active excipients. This suggests that formulation principles using preferentially interacting excipients are similar for PEGylated and non-PEGylated proteins.

U2 - 10.1371/journal.pone.0133584

DO - 10.1371/journal.pone.0133584

M3 - Journal article

VL - 10

JO - P L o S One

JF - P L o S One

SN - 1932-6203

IS - 7

M1 - e0133584

ER -

ID: 143083709