Effect of polyethylene glycol conjugation on conformational and colloidal stability of a monoclonal antibody antigen-binding fragment (Fab').
作者： Cristopher Roque , Anthony Sheung , Nausheen Rahman , S. Fernando Ausar
DOI: 10.1021/MP500658W
关键词: Biophysics 、 PEGylation 、 Fluorescence spectroscopy 、 Absorbance 、 Circular dichroism 、 Monoclonal antibody 、 Chemistry 、 Ultraviolet 、 Polyethylene glycol 、 Colloid 、 Chromatography
摘要: We have investigated the effects of site specific “hinge” polyethylene glycol conjugation (PEGylation) on thermal, pH, and colloidal stability a monoclonal antibody antigen-binding fragment (Fab′) using variety biophysical techniques. The results obtained by circular dichroism (CD), ultraviolet (UV) absorbance, fluorescence spectroscopy suggested that physical Fab′ is maximized at pH 6–7 with no apparent differences due to PEGylation. Temperature-induced aggregation experiments revealed PEGylation was able increase transition temperature, as well prevent formation visible subvisible aggregates. Statistical comparison three-index empirical phase diagram (EPD) significant in thermal signatures between PEG-Fab′. Upon mechanical stress, micro-flow imaging (MFI) measurement optical density 360 nm showed PEG-Fab′ had significantly higher resistance surface-induced aggregatio...
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