کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2487769 | 1114431 | 2007 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Effects of Solutes on Empirical Phase Diagrams of Human Fibroblast Growth Factor 1
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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
A variety of solutes are commonly used to increase the stability of protein in therapeutic formulations. An empirical phase diagram approach is used to evaluate the effects of different types of additives on the solution behavior of a protein of pharmaceutical interest, human fibroblast growth factor 1 (FGFâ1). A specific stabilizer, heparin, and a nonspecific stabilizer, sucrose, were used in this work. The protein was characterized as a function of pH (3-8) and temperature (10-85°C) using FarâUV circular dichroism (FarâUV CD), intrinsic and extrinsic fluorescence as well as second derivative UV absorption spectroscopy. Empirical phase diagrams were constructed to summarize the biophysical characterization data obtained with FGFâ1 alone, in the presence of a threefold weight excess of heparin (3à heparin) or 10% sucrose (w/v). Three phases are observed in the low temperature regions at pH 3, 4, and 5-8. Phase boundaries corresponding to major heatâinduced transitions are detected in the physiological temperature range. The highest thermal stabilities are observed near neutral pH (pH 6 and 7). Both heparin and sucrose appear to enhance the thermal stability of FGFâ1, although their effects on the phase diagram are quite distinct. The greatest stabilization is observed at pH 8. Only heparin appears to protect FGFâ1 from acidâinduced unfolding to any extent.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 96, Issue 6, June 2007, Pages 1490-1503
Journal: Journal of Pharmaceutical Sciences - Volume 96, Issue 6, June 2007, Pages 1490-1503
نویسندگان
Haihong Fan, Huaina Li, Mingyu Zhang, C.Russell Middaugh,