Biophysical study of bevacizumab structure and bioactivity under thermal and pH-stresses

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
Flávia SousaMaria Teresa Neves-Petersen

Abstract

The evaluation of the structural stability and bioactivity of monoclonal antibodies (mAb) is a crucial step in the development of mAb therapeutic based products, since immunogenicity needs to be avoided. In the present work, a study was carried out to understand the changes on the structure and bioactivity of mAbs induced by different pH and temperature values. Structural changes of bevacizumab were monitored using fluorescence spectroscopy, circular dichroism (CD) and Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR). The secondary and tertiary structural content was monitored at six different pH values and at room temperature, upon heating up to 85°C and upon cooling down to 20°C. Furthermore, the temperature induced conformational changes were continuously monitored from 20°C to 85°C using fluorescence spectroscopy and circular dichroism, allowing to monitor the melting temperature of the protein at different pH values. The results showed that the thermal denaturation of bevacizumab was irreversible at all pH value. The conformational changes induced by pH were higher at extreme pH values (5, 9 and 10) than neutral pH. Thermal stability studies showed that pH6 was the pH that confer bevacizumab ...Continue Reading

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Citations

May 31, 2021·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Marieke E Klijn, Jürgen Hubbuch
Sep 2, 2018·International Journal of Biological Macromolecules·Osmar Soares da SilvaTatiana Souza Porto
Sep 18, 2021·Preparative Biochemistry & Biotechnology·José Manoel Wanderley Duarte NetoAna Lúcia Figueiredo Porto

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