کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2486611 | 1114388 | 2011 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Plain and Mono-pegylated Recombinant Human Insulin Exhibit Similar Stress-Induced Aggregation Profiles
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
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![عکس صفحه اول مقاله: Plain and Mono-pegylated Recombinant Human Insulin Exhibit Similar Stress-Induced Aggregation Profiles Plain and Mono-pegylated Recombinant Human Insulin Exhibit Similar Stress-Induced Aggregation Profiles](/preview/png/2486611.png)
چکیده انگلیسی
PEGylation has been suggested to improve the stability of insulin, but evidence for that is scarce. Here, we compared the forced aggregation behavior of insulin and mono-PEGylated insulin. Therefore, recombinant human insulin was conjugated on lysine B29 with 5-kDa PEG. PEG-insulin was purified by size-exclusion chromatography (SEC) and characterized by mass spectrometry (MS). Next, insulin and PEG-insulin were subjected to heating at 75°C, metal-catalyzed oxidation, and glutaraldehyde cross-linking. The products were characterized physicochemically by complementary analytical methods. Mono-PEGylation of insulin was confirmed by SEC and MS. Under each of the applied stress conditions, insulin and PEG-insulin showed comparable degradation profiles. All the stressed samples showed submicron aggregates in the size range between 50 and 500 nm. Covalent aggregates and conformational changes were found for both oxidized products. Insulin and its PEGylated counterpart also exhibited similar characteristics when exposed to heat stress, that is, slightly changed secondary and tertiary structures, covalent aggregates with partially intact epitopes, and separation of chain A from chain B. Both glutaraldehyde-treated insulin and PEG-insulin contained covalent and noncovalent aggregates with intact epitopes, showed partially perturbed secondary structure, and substantial loss of tertiary structure. From these results, we conclude that PEGylation does not protect insulin against forced aggregation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 100, Issue 7, July 2011, Pages 2574-2585
Journal: Journal of Pharmaceutical Sciences - Volume 100, Issue 7, July 2011, Pages 2574-2585
نویسندگان
Riccardo Torosantucci, Basak Kukrer, Anna Mero, Margot Van Winsen, Ruedeeporn Tantipolphan, Wim Jiskoot,