کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
35299 45085 2009 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
PEGylation of rhIL-1RA increased its solution stability at room temperature
موضوعات مرتبط
مهندسی و علوم پایه مهندسی شیمی بیو مهندسی (مهندسی زیستی)
پیش نمایش صفحه اول مقاله
PEGylation of rhIL-1RA increased its solution stability at room temperature
چکیده انگلیسی

Recombinant human interleukin-1 receptor antagonist (rhIL-1RA) is an important cytokine in the treatment of inflammatory diseases. However, it is instable in aqueous solution and prone to degrade without the addition of any excipient. Following the 30- or 60-day storage in 50 mM sodium acetate (pH 5.0) at room temperature, rhIL-1RA markedly degraded into three species (denoted as P1, P2 and P3 in this study), the bioactivities of which to a different extent was lost (from 9.72 × 104 UI/mg to 3.07 × 103 UI/mg for P1, 5.49 × 103 UI/mg for P2, 1.09 × 104 UI/mg for P3, respectively). To solve this problem, we prepared the mono-PEGylated rhIL-1RA with propionaldehyde mPEG (ALD-PEG, Mw 5000 Da). The conjugate showed more favorable stability than original protein, and remained homogeneous under the similar storage conditions. In addition, the activity of the conjugate was well retained (from 5.80 × 104 UI/mg to 4.92 × 104 UI/mg), compared to that of original protein. The results based on the combination analysis of CD, ion exchange chromatography and RP-HPLC, revealed that the stability improvement of rhIL-1RA majorly benefited from the PEG strands protection against the protein conformational changes occurred during the storage.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Process Biochemistry - Volume 44, Issue 12, December 2009, Pages 1340–1345
نویسندگان
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