کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2485801 | 1114367 | 2011 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
BIOTECHNOLOGY: Aggregation of Recombinant Human Botulinum Protein Antigen Serotype C in Varying Solution Conditions: Implications of Conformational Stability for Aggregation Kinetics
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کلمات کلیدی
protein aggregation - تجمع پروتئینThermodynamics - ترمودینامیکcircular dichroism - رنگ تابی دورانیProtein structure - ساختار پروتئینProtein formulation - فرمول پروتئینFormulation - فرمولاسیونFluorescence spectroscopy - فوتولومینسانس یا فلوئورسانس یا فسفرسانسBiophysical models - مدل های بیوفیزیکیprotein folding/refolding - پروتئین تاشو / انجمادSolution calorimetry - کالری سنجی محلول
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Solution conditions greatly affect the aggregation rate of a protein. Elucidating these influences provides insight into the critical factors governing aggregation. In this study, recombinant human botulinum protein antigen serotype C [rBoNTC (Hc)] was employed as a model protein. rBoNTC (Hc) aggregated irreversibly during incubation at 42°C. The aggregation rate was studied as a function of solution conditions, including varying the pH from 3.5 to 8.0 and with or without 150 mM NaCl, 7.5% (w/v) trehalose, and 0.5 M urea. Some solution conditions retarded rBoNTC (Hc) aggregation, whereas others accelerated aggregation, particularly acidic pH and addition of NaCl or urea. To better understand the mechanism by which these solution conditions influenced aggregation rates, the structure of rBoNTC (Hc) was characterized using circular dichroism, fluorescence, and ultraviolet absorbance spectroscopies. Conformational stability was assessed from equilibrium urea-induced unfolding studies and by using differential scanning calorimetry (DSC). The activation energy of the aggregation reaction (Ea) was estimated from an analysis of the heating-rate dependence of the thermal transition observed during DSC heating scans. Overall, for rBoNTC (Hc), an inverse correlation was found between conformational stability and aggregation rate, as well as between the kinetic barrier to unfolding (i.e., Ea) and aggregation rate.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 100, Issue 3, March 2011, Pages 836-848
Journal: Journal of Pharmaceutical Sciences - Volume 100, Issue 3, March 2011, Pages 836-848
نویسندگان
Shujun Bai, Mark Cornell Manning, Theodore W. Randolph, John F. Carpenter,