کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1938893 1050749 2007 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A broad range of Fab stabilities within a host of therapeutic IgGs
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
A broad range of Fab stabilities within a host of therapeutic IgGs
چکیده انگلیسی

Although the functional properties of IgGs are well known, little has been published concerning the stability of whole IgG molecules. Stability is, however, a requirement for the development of antibodies for therapeutic or diagnostic applications. The hypervariable antigen-binding region (Fv) is responsible for stability variations between IgGs of identical subclass. To determine the range of stabilities that may be expected for human(ized) antibodies, differential scanning calorimetry was performed on 17 human(ized) antibodies from various in-house programs. The antigen-binding fragments (Fabs) of these antibodies exhibited thermal unfolding transitions with midpoints (TMs) varying from 57 to 82 °C. Antibodies with very low Fab stabilities were found to aggregate and express poorly. Fab instability was often associated with high levels of uncommonly observed amino acids or CDR loop lengths particularly within the variable heavy chain domain. Overall, the study provides a thermostability range for IgGs and suggests possible stability guidelines for developing antibody diagnostics or therapeutics.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 355, Issue 3, 13 April 2007, Pages 751–757
نویسندگان
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