Biotechnology Letters, 2016, Vol.38(4), pp.589-596
To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1007/s10529-015-2014-y Byline: Evdoxia Gourbatsi (1), Jane Povey (1), Shahid Uddin (2), C. Mark Smales (1) Keywords: Protein formulation; Mass spectrometry; Post-translational modification; Aggregation; Peptide model Abstract: Objectives The effect of different formulations variables on protein integrity were investigated using lysozyme as a model protein for the development of biotherapeutic protein formulations for use in the clinic. Results Buffer composition/concentration was the key variable of formulation reagents investigated in determining lysozyme stability and authenticity independent of protein concentration whilst the storage temperature and time, not surprisingly, were also key variables. Tryptic peptide mapping of the protein showed that the modifications occurred when formulated under specific conditions but not others. A model peptide system was developed that reflected the same behavior under formulation conditions as intact lysozyme. Conclusions Peptide models may mirror the stability of proteins, or regions of proteins, in the same formulations and be used to help develop a rapid screen of formulations for stabilisation of biotherapeutic proteins. Author Affiliation: (1) School of Biosciences and Centre for Molecular Processing, University of Kent, Canterbury, CT2 7NJ, UK (2) Formulation Sciences, AKB Building, MedImmune, Granta Park, Cambridge, CB21 6GH, UK Article History: Registration Date: 07/12/2015 Received Date: 05/11/2015 Accepted Date: 02/12/2015 Online Date: 23/12/2015 Article note: Electronic supplementary material The online version of this article (doi: 10.1007/s10529-015-2014-y) contains supplementary material, which is available to authorized users.
Protein formulation ; Mass spectrometry ; Post-translational modification ; Aggregation ; Peptide model
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