کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2486866 | 1114396 | 2008 | 18 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Effect of PEGylation on the Solution Conformation of Antibody Fragments
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
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چکیده انگلیسی
Covalent attachment of poly(ethylene glycol) (PEG) to therapeutic antibody fragments has been found effective in prolonging the half-life of the protein molecule in vivo. In this study analytical ultracentrifugation (AUC) in combination with small angle X-ray scattering (SAXS) has been applied to a number of antibody fragments and to their respective PEGylated conjugates. Despite the large increase in molecular weight due to the attachment of a 20-40Â kDa PEG moiety, the PEGylated conjugates have smaller sedimentation coefficients, s, than their parent antibody fragments, due to a significant increase in frictional ratio f/fo (from ~1.3 to 2.3-2.8): the solution hydrodynamic properties of the conjugates are clearly dominated by the PEG moiety (f/fo ~3.0). This observation is reinforced by SAXS data at high values of r (separation of scattering centres within a particle) that appear dominated by the PEG part of the complex. By contrast, SAXS data at low values of r suggest that there are no significant conformational changes of the protein moiety itself after PEGylation The location of the PEGylation site within the conjugate was identified, and found to be consistent with expectation from the conjugation chemistry.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 97, Issue 6, June 2008, Pages 2062-2079
Journal: Journal of Pharmaceutical Sciences - Volume 97, Issue 6, June 2008, Pages 2062-2079
نویسندگان
Yanling Lu, Stephen E. Harding, Alison Turner, Bryan Smith, Diljeet S. Athwal, J.Günter Grossmann, Kenneth G. Davis, Arthur J. Rowe,