Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2485282 | Journal of Pharmaceutical Sciences | 2011 | 10 Pages |
Abstract
Benzyl alcohol, a preservative commonly added to multidose therapeutic protein formulations, can accelerate aggregation of recombinant human interleukin-1 receptor antagonist (rhIL-1ra). To investigate the interactions between benzyl alcohol and rhIL-1ra, we used nuclear magnetic resonance to observe the effect of benzyl alcohol on the chemical shifts of amide resonances of rhIL-1ra and to measure hydrogen-deuterium exchange rates of individual rhIL-1ra residues. Additionof 0.9% benzyl alcohol caused significant chemical shifts of amide resonances for residues 90-97, suggesting that these solvent-exposed residues participate in the binding of benzyl alcohol. In contrast, little perturbation of exchange rates was observed in the presence of either sucrose or benzyl alcohol. © 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:4215-4224, 2011
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Authors
John R. Alford, Andrew C. Fowler, Deborah S. Wuttke, Bruce A. Kerwin, Ramil F. Latypov, John F. Carpenter, Theodore W. Randolph,