The influence of charge distribution on self-association and viscosity behavior of monoclonal antibody solutions

Molecular Pharmaceutics
Sandeep YadavSteven J Shire

Abstract

The present work investigates the influence of electrostatic surface potential distribution of monoclonal antibodies (MAbs) on intermolecular interactions and viscosity. Electrostatic models suggest MAb-1 has a less uniform surface charge distribution than MAb-2. The patches of positive and negative potential on MAb-1 are predicted to favor intermolecular attraction, even in the presence of a small net positive charge. Consistent with this expectation, MAb-1 exhibits a negative second virial coefficient (B₂₂), an increase in static structure factor, S((q→0)), and a decrease in hydrodynamic interaction parameter, H((q→0)), with increase in MAb-1 concentration. Conversely, MAb-2 did not show such heterogeneous charge distribution as MAb-1 and hence favors intermolecular repulsion (positive B₂₂), lower static structure factor, S((q→0)), and repulsion induced increase in momentum transfer, H((q→0)), to result in lower viscosity of MAb-2. Charge swap mutants of MAb-1, M-5 and M-7, showed a decrease in charge asymmetry and concomitantly a loss in self-associating behavior and lower viscosity than MAb-1. However, replacement of charge residues in the sequence of MAb-2, M-10, did not invoke charge distribution to the same extent as MAb...Continue Reading

References

Feb 1, 1994·Molecular Immunology·E A Padlan
Apr 1, 1993·Applied Biochemistry and Biotechnology·H H Weetall, A K Gaigalas
Aug 27, 1998·Electrophoresis·T M RidgewayT M Laue
Sep 29, 1998·Methods in Enzymology·T M LaueT J Wilson
Aug 23, 2001·Proceedings of the National Academy of Sciences of the United States of America·N A BakerJ A McCammon
Mar 22, 2003·Protein Science : a Publication of the Protein Society·Jason G S HoHans P Kocher
Apr 30, 2003·Journal of Structural Biology·W William Wilson
Jun 26, 2003·Nucleic Acids Research·Narayanan EswarAndrej Sali
May 5, 2004·Journal of Pharmaceutical Sciences·Steven J ShireJun Liu
Jun 25, 2004·Nucleic Acids Research·Todd J DolinskyNathan A Baker
Jul 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·A George, W W Wilson
Nov 27, 2004·Nature·Anna StradnerPeter Schurtenberger
Dec 29, 2004·Analytical Biochemistry·Thomas P MoodyThomas M Laue
Jan 25, 2005·Biophysical Journal·Eric J Sorin, Vijay S Pande
Jun 8, 2007·Nucleic Acids Research·Thomas M KeaneJames O McInerney
Mar 26, 2008·Proceedings of the National Academy of Sciences of the United States of America·Anuj ShuklaDmitri I Svergun
May 29, 2009·Journal of Pharmaceutical Sciences·Branden A SalinasTheodore W Randolph
Aug 26, 2009·Journal of Pharmaceutical Sciences·Sandeep YadavDevendra S Kalonia
Sep 8, 2010·Journal of Pharmaceutical Sciences·Sandeep YadavDevendra S Kalonia
Jan 20, 2011·Biotechnology and Bioengineering·Wei Du, Alexander M Klibanov
Apr 15, 2011·Pharmaceutical Research·Sandeep YadavDevendra S Kalonia
May 19, 2011·Nature Chemical Biology·Tom Laue, Borries Demeler
Jan 21, 2012·Pharmacognosy Magazine·Jin-Won ChungSung-Jin Kim

❮ Previous
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Citations

Oct 29, 2013·The Journal of Chemical Physics·P Douglas GodfrinNorman J Wagner
Feb 25, 2014·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Andrea AllmendingerRobert Mueller
Aug 1, 2014·Journal of Pharmaceutical and Biomedical Analysis·Andrea AllmendingerJörg Huwyler
Mar 19, 2014·Pharmaceutical Research·Shubhadra N SinghDevendra S Kalonia
Jul 23, 2013·Journal of Pharmaceutical Sciences·Isidro E ZarragaFredric J Lim
Nov 20, 2014·Journal of Pharmaceutical Sciences·Reza EsfandiaryHasige Sathish
Sep 12, 2014·Journal of Pharmaceutical Sciences·Steven B GengPeter M Tessier
Mar 31, 2015·Journal of Pharmaceutical Sciences·Alexander JaraschHubert Kettenberger
Oct 22, 2013·Journal of Pharmaceutical Sciences·Weiqiang ChengC Russell Middaugh
Nov 26, 2013·Journal of Bioscience and Bioengineering·Naoto InoueKentaro Shiraki
Apr 30, 2013·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Martin S NeergaardMarco van de Weert
Feb 26, 2016·Pharmaceutical Research·Qiu DanwenDamian Houde
Sep 26, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Adrian B LiDavid L Kaplan
Oct 13, 2015·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Patrick GaridelSven Bahrenburg
Sep 22, 2015·The Journal of Physical Chemistry. B·Thomas M Scherer
May 20, 2015·Pharmaceutical Research·Satish K SinghRoger H Pak
Sep 4, 2015·The Journal of Chemical Physics·Cecilia BoresNoé G Almarza
Jul 25, 2015·The Journal of Physical Chemistry. B·Dejan ArzenšekRudolf Podgornik
Aug 19, 2014·Biochimica Et Biophysica Acta·Susumu Uchiyama
Apr 3, 2015·Pharmaceutical Research·Elaheh BinabajiAndrew L Zydney
Jun 20, 2013·MAbs·Isidro HötzelRobert F Kelley
Feb 28, 2013·Biophysical Journal·Jai A PathakRojaramani Narwal
Nov 26, 2013·Biophysical Journal·Prasad S SarangapaniJai A Pathak
Jul 5, 2016·Journal of Pharmaceutical Sciences·Teng-Chieh YangWei Wang
Jun 20, 2013·Bioconjugate Chemistry·Nicholas J BoylanJennifer S Laurence

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