کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10161957 | 1114307 | 2015 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Influence of Tableting on the Conformation and Thermal Stability of Trypsin as a Model Protein
ترجمه فارسی عنوان
تأثیر قرص بر روی سازگاری و پایداری حرارتی تریپسین به عنوان پروتئین مدل
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کلمات کلیدی
Protein folding - تاشدگی پروتئینPrincipal component analysis - تحلیل مولفههای اصلی یا PCAMultivariate analysis - تحلیل چندمتغیرهCompaction - تراکمsolid-state stability - ثبات حالت جامدPartial least squares - حداقل مربعات جزئی Protein structure - ساختار پروتئینFTIR - طیف سنج مادون قرمزCompression - فشرده سازیTableting - قرص
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
چکیده انگلیسی
The objective of this study was to investigate the influence of compaction on the conformation of trypsin, its transition temperature (Tm) of unfolding, and its folding reversibility after thermal denaturation. Plain trypsin was compacted at 40-382Â MPa. Pressure-induced changes in the trypsin conformation and the extent of their reversibility were determined using solid- and liquid-state IR spectroscopy together with principal component analysis and an area overlap approach. Trypsin enzymatic activity was determined by a photometric assay. Liquid-state differential scanning calorimetry was performed to determine the Tm as well as the folding reversibility after thermal denaturation of the reconstituted samples. It was found that compacted samples showed reduced activity accompanied by an altered secondary structure. Conformational changes that occur in the solid state were partially reversible upon tablet reconstitution. Aqueous-state IR spectroscopy combined with partial least squares was shown to be a powerful tool to follow irreversible structural changes and evaluate sample bioactivity. Besides its conformation, the thermal stability of trypsin was altered as a result of the applied compaction pressure, indicated by a reduced folding reversibility. In conclusion, this study reveals that tableting can have a negative impact on the biological quality of protein APIs. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 104, Issue 12, December 2015, Pages 4314-4321
Journal: Journal of Pharmaceutical Sciences - Volume 104, Issue 12, December 2015, Pages 4314-4321
نویسندگان
Marten Klukkert, Marco van de Weert, Mathias Fanø, Thomas Rades, Claudia S. Leopold,