کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10162147 | 1114317 | 2015 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Technical Decision Making with Higher Order Structure Data: Utilization of Differential Scanning Calorimetry to Elucidate Critical Protein Structural Changes Resulting from Oxidation
ترجمه فارسی عنوان
تصمیم گیری فنی با داده های ساختاری بالاتر: استفاده از کالوریمتری اسکن دیفرانسیل برای تبیین تغییرات ساختاری پروتئین انتقادی ناشی از اکسیداسیون
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
چکیده انگلیسی
Differential scanning calorimetry (DSC) is a useful tool for monitoring thermal stability of the molecular conformation of proteins. Here, we present an example of the sensitivity of DSC to changes in stability arising from a common chemical degradation pathway, oxidation. This Note is part of a series of industry case studies demonstrating the application of higher order structure data for technical decision making. For this study, six protein products from three structural classes were evaluated at multiple levels of oxidation. For each protein, the melting temperature (Tm) decreased linearly as a function of oxidation; however, differences in the rate of change in Tm, as well as differences in domain Tm stability were observed across and within structural classes. For one protein, analysis of the impact of oxidation on protein function was also performed. For this protein, DSC was shown to be a leading indicator of decreased antigen binding suggesting a subtle conformation change may be underway that can be detected using DSC prior to any observable impact on product potency. Detectable changes in oxidized methionine by mass spectrometry (MS) occurred at oxidation levels below those with a detectable conformational or functional impact. Therefore, by using MS, DSC, and relative potency methods in concert, the intricate relationship between a primary structural modification, changes in conformational stability, and functional impact can be elucidated.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 104, Issue 4, April 2015, Pages 1548-1554
Journal: Journal of Pharmaceutical Sciences - Volume 104, Issue 4, April 2015, Pages 1548-1554
نویسندگان
Kelly K. Arthur, Nikita Dinh, John P. Gabrielson,