کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2484742 | 1114331 | 2013 | 16 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Correlating Excipient Effects on Conformational and Storage Stability of an IgG1 Monoclonal Antibody with Local Dynamics as Measured by Hydrogen/Deuterium-Exchange Mass Spectrometry
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کلمات کلیدی
Monoclonal antibody - آنتی بادی مونوکلونالSize-exclusion chromatography - اندازه گیری کروماتوگرافی حذف شدهFlexibility - انعطاف پذیریHydrogen/deuterium exchange - تبادل هیدروژن / دایتریمStability - ثباتBackbone dynamics - دینامیک ستون فقراتMass spectrometry - طیف سنجی جرمیExcipients - عضلاتFormulation - فرمولاسیونCalorimetry (DSC) - کالریمتری (DSC)
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
The effects of sucrose and arginine on the conformational and storage stability of an IgG1 monoclonal antibody (mAb) were monitored by differential scanning calorimetry (DSC) and size-exclusion chromatography (SEC), respectively. Excipient effects on protein physical stability were then compared with their effects on the local flexibility of the mAb in solution at pH 6, 25°C using hydrogen/deuterium-exchange mass spectrometry (H/D-MS). Compared with a 0.1 M NaCl control, sucrose (0.5 M) increased conformational stability (Tm values), slowed the rate of monomer loss, reduced the formation of insoluble aggregates, and resulted in a global trend of small decreases in local flexibility across most regions of the mAb. In contrast, the addition of arginine (0.5 M) decreased the mAb's conformational stability, increased the rate of loss of monomer with elevated levels of soluble and insoluble aggregates, and led to significant increases in the local flexibility in specific regions of the mAb, most notably within the constant domain 2 of the heavy chain (CH2). These results provide new insights into the effect of sucrose and arginine on the local dynamics of IgG1 domains as well as preliminary correlations between local flexibility within specific segments of the CH2 domain (notably heavy chain 241-251) and the mAb's overall physical stability. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:2136-2151, 2013
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 102, Issue 7, July 2013, Pages 2136-2151
Journal: Journal of Pharmaceutical Sciences - Volume 102, Issue 7, July 2013, Pages 2136-2151
نویسندگان
Prakash Manikwar, Ranajoy Majumdar, John M. Hickey, Santosh V. Thakkar, Hardeep S. Samra, Hasige A. Sathish, Steven M. Bishop, C. Russell Middaugh, David D. Weis, David B. Volkin,