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Progress and Challenges in PEGylated Proteins Downstream Processing: A Review of the Last 8 Years

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Abstract

PEGylation is a well-known process in the bio-pharmaceutical industry mainly due to its great performance in increasing blood circulation half-life of peptides and proteins for health purposes. More than 40 years have been devoted to the study of derived products from PEGylation reaction [native, mono-, di-, multi- PEGylated proteins and unreacted poly(ethylene glycol) (PEG)]. Despite the lack of selectivity and randomness of PEG chains attachment have been overcome by site-specific PEGylation, several drugs that are currently in the market are obtained by means of random PEGylation. In the context of downstream processing, separation of mono-PEGylated forms and their isomers is still a challenge. The growing demand of PEGylated drugs in the pharmaceutical industry requires simple, robust, cost effective and efficient methods for the purification process. The aim of this review is to provide an updated revision along the last 8 years of the methods for the fractionation of PEGylated proteins relative to other contaminant proteins, n-PEGylated forms and their isomers. Chromatographic methods including size exclusion, ion exchange, reversed phase HPLC and affinity have been enlisted. Non-chromatographic complementary techniques such as aqueous two-phase systems and electrophoresis also have been included in this compilation.

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Acknowledgements

The authors would like to thank the Bioprocess Research Chair (0020209I13), the FEMSA Biotechnology Center and the School of Engineering and Science at Tecnológico de Monterrey for their support. Ana Mayela Ramos-de-la-Peña, would also like to thank the National Council of Science and Technology of Mexico (CONACYT) for her Postdoctoral Grant.

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  1. School of Engineering and Science, Tecnologico de Monterrey, Av. Eugenio Garza Sada 2501 Sur, 64849, Monterrey, NL, Mexico

    Ana Mayela Ramos-de-la-Peña & Oscar Aguilar

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  1. Ana Mayela Ramos-de-la-Peña
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  2. Oscar Aguilar
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All authors have agreed to be named as authors on this manuscript. Any work (data, text, or theories) of others besides the authors has been properly acknowledged. The work is original and not previously published. All data are true and accurate to the knowledge of the authors.

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Ramos-de-la-Peña, A.M., Aguilar, O. Progress and Challenges in PEGylated Proteins Downstream Processing: A Review of the Last 8 Years. Int J Pept Res Ther 26, 333–348 (2020). https://doi.org/10.1007/s10989-019-09840-4

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