کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2486609 | 1114388 | 2011 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Assessment of Net Charge and Protein-Protein Interactions of Different Monoclonal Antibodies
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
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چکیده انگلیسی
The purpose of this work was to compare biophysical properties of different monoclonal antibodies (mAbs). mAbs' theoretical isoelectric point (IEP) and theoretical net charge were compared with experimentally assessed values. IEP was determined by isoelectric focusing capillary electrophoresis, determination of zero electrophoretic mobility, or the minimum mutual diffusion coefficient during pH titration. Net charge was determined using electrophoretic mobility and self-diffusion coefficient. It was found that antibodies differ substantially in their biophysical properties, that is, in IEP, net charge, and zeta potential. Also, the importance of these properties was studied with respect to protein-protein interactions. This was achieved by assessing the second virial coefficient (A2) determined by static light scattering (SLS) and dynamic light scattering (DLS). It was found that at low ionic strength formulation conditions [20Â mM histidine (His)/His-HCl buffer, pH 6.0] proteins' charge is the main driver for overall repulsive protein interactions. At high ionic strength conditions (20Â mM His/His-HCl buffer, pH 6.0, + 150Â mM NaCl), where counterions are shielding ionic interactions, proteins' repulsive forces were weakened, but to a different extent. Furthermore, a DLS method was developed allowing fast and easy assessment of A2 by minimum need of material.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 100, Issue 7, July 2011, Pages 2551-2562
Journal: Journal of Pharmaceutical Sciences - Volume 100, Issue 7, July 2011, Pages 2551-2562
نویسندگان
Christian Lehermayr, Hanns-Christian Mahler, Karsten Mäder, Stefan Fischer,