کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2485986 | 1114372 | 2012 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Antibody Solubility Behavior in Monovalent Salt Solutions Reveals Specific Anion Effects at Low Ionic Strength
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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
Protein solubility was measured using the crystalline precipitate of a recombinant therapeutic antibody, in monovalent salt solutions containing KF, KCl, and KSCN (up to â¼0.7 M) at different pH conditions. For all three anions, the antibody solubility demonstrated complex behavior, both monotonic and nonmonotonic, with dependence on pH and salt concentration. At pH 7.1, close to the isoelectric point (pI) of 7.2, a typical salting-in behavior was observed with the salting-in constants of 12.7, 8.0, and 2.8Â M for KSCN, KCl, and KF, respectively, suggesting that the anions follow the order of SCNâ > Clâ > Fâ for increasing antibody solubility. Nonmonotonic behavior, as described by an initial solubility decrease followed by a solubility increase with ionic strength, was observed at pH 5.3, far below its pI. The effectiveness of the anion for reducing the solubility followed the order of SCNâ > Clâ > Fâ. After the solubility reached the minimum, the anion's effectiveness for raising the antibody solubility was in agreement with that at pH 7.1. The mechanisms for the above phenomena are discussed based upon specific binding of the anions to the antibody surface. The mechanistic view of anion binding and its charge neutralization effect at pH 5.3 was supported by the results from the effective charge and zeta-potential measurements.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 101, Issue 3, March 2012, Pages 965-977
Journal: Journal of Pharmaceutical Sciences - Volume 101, Issue 3, March 2012, Pages 965-977
نویسندگان
Le Zhang, Helming Tan, R. Matthew Fesinmeyer, Cynthia Li, David Catrone, David Le, Richard L. Jr., Jifeng Zhang,