The mPEG-aldehyde PEGylation with two different PEG sizes and two proteins was experimentally determined with respect to yield, conversion, and selectivity. The kinetic behavior of these PEGylation reactions was simulated using a numerically solved set of differential equations. We show that the assumption of an inactivation of mPEG-aldehyde is crucial for the simulation of the overall PEGylation and that the inactivation is pH-dependent. We further demonstrate that ideal PEGylation parameters such as pH, temperature, reaction time, and protein concentration need to be chosen carefully depending on the protein and PEG size. In terms of selectivity and yield, we show that the reaction should be stopped before the highest mono-PEG concentration is reached. Moreover, room temperature and a slightly acidic pH of approximately 6 are good starting points. In conclusion, selectivity can be optimized choosing a shorter reaction time and a reduced reaction temperature.
Moosmann, Anna
Blath, Jessica
Lindner, Robert
Muller, Egbert
Bottinger, Heiner
eng
Research Support, Non-U.S. Gov't
Bioconjug Chem. 2011 Aug 17;22(8):1545-58. doi: 10.1021/bc200090x. Epub 2011 Aug 1.
%0 Journal Article
%1 Moosmann2011
%A Moosmann, Anna
%A Blath, Jessica
%A Lindner, Robert
%A Müller, Egbert
%A Böttinger, Heiner
%D 2011
%J Bioconjugate Chemistry
%K 2011 boettinger izi
%N 8
%P 1545--1558
%R 10.1021/bc200090x
%T Aldehyde PEGylation kinetics: A standard protein versus a pharmaceutically relevant single chain variable fragment
%U https://www.ncbi.nlm.nih.gov/pubmed/21780828
%V 22
%X The mPEG-aldehyde PEGylation with two different PEG sizes and two proteins was experimentally determined with respect to yield, conversion, and selectivity. The kinetic behavior of these PEGylation reactions was simulated using a numerically solved set of differential equations. We show that the assumption of an inactivation of mPEG-aldehyde is crucial for the simulation of the overall PEGylation and that the inactivation is pH-dependent. We further demonstrate that ideal PEGylation parameters such as pH, temperature, reaction time, and protein concentration need to be chosen carefully depending on the protein and PEG size. In terms of selectivity and yield, we show that the reaction should be stopped before the highest mono-PEG concentration is reached. Moreover, room temperature and a slightly acidic pH of approximately 6 are good starting points. In conclusion, selectivity can be optimized choosing a shorter reaction time and a reduced reaction temperature.
%Z Moosmann, Anna
Blath, Jessica
Lindner, Robert
Muller, Egbert
Bottinger, Heiner
eng
Research Support, Non-U.S. Gov't
Bioconjug Chem. 2011 Aug 17;22(8):1545-58. doi: 10.1021/bc200090x. Epub 2011 Aug 1.
%7 2011/07/26
%@ 0086222740
@article{Moosmann2011,
abstract = {The mPEG-aldehyde PEGylation with two different PEG sizes and two proteins was experimentally determined with respect to yield, conversion, and selectivity. The kinetic behavior of these PEGylation reactions was simulated using a numerically solved set of differential equations. We show that the assumption of an inactivation of mPEG-aldehyde is crucial for the simulation of the overall PEGylation and that the inactivation is pH-dependent. We further demonstrate that ideal PEGylation parameters such as pH, temperature, reaction time, and protein concentration need to be chosen carefully depending on the protein and PEG size. In terms of selectivity and yield, we show that the reaction should be stopped before the highest mono-PEG concentration is reached. Moreover, room temperature and a slightly acidic pH of approximately 6 are good starting points. In conclusion, selectivity can be optimized choosing a shorter reaction time and a reduced reaction temperature.},
added-at = {2018-02-01T14:56:48.000+0100},
annote = {Moosmann, Anna
Blath, Jessica
Lindner, Robert
Muller, Egbert
Bottinger, Heiner
eng
Research Support, Non-U.S. Gov't
Bioconjug Chem. 2011 Aug 17;22(8):1545-58. doi: 10.1021/bc200090x. Epub 2011 Aug 1.},
author = {Moosmann, Anna and Blath, Jessica and Lindner, Robert and M{\"{u}}ller, Egbert and B{\"{o}}ttinger, Heiner},
biburl = {https://puma.ub.uni-stuttgart.de/bibtex/2836a77bb0abc210beb7e5184837b22a2/cristiano},
doi = {10.1021/bc200090x},
edition = {2011/07/26},
interhash = {9e48e448e75575d525cf2694217d4b90},
intrahash = {836a77bb0abc210beb7e5184837b22a2},
isbn = {0086222740},
issn = {10431802},
journal = {Bioconjugate Chemistry},
keywords = {2011 boettinger izi},
number = 8,
pages = {1545--1558},
pmid = {21780828},
timestamp = {2018-07-25T12:32:22.000+0200},
title = {{Aldehyde PEGylation kinetics: A standard protein versus a pharmaceutically relevant single chain variable fragment}},
url = {https://www.ncbi.nlm.nih.gov/pubmed/21780828},
volume = 22,
year = 2011
}