An open-source automated PEG precipitation assay to measure the relative solubility of proteins with low material requirement.
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Publication Date
2021-11-09Journal Title
Sci Rep
ISSN
2045-2322
Publisher
Springer Science and Business Media LLC
Volume
11
Issue
1
Pages
21932
Language
eng
Type
Article
This Version
AM
Metadata
Show full item recordCitation
Oeller, M., Sormanni, P., & Vendruscolo, M. (2021). An open-source automated PEG precipitation assay to measure the relative solubility of proteins with low material requirement.. Sci Rep, 11 (1), 21932. https://doi.org/10.1038/s41598-021-01126-4
Abstract
The solubility of proteins correlates with a variety of their properties, including function, production yield, pharmacokinetics, and formulation at high concentrations. High solubility is therefore a key requirement for the development of protein-based reagents for applications in life sciences, biotechnology, diagnostics, and therapeutics. Accurate solubility measurements, however, remain challenging and resource intensive, which limits their throughput and hence their applicability at the early stages of development pipelines, when long-lists of candidates are typically available in minute amounts. Here, we present an automated method based on the titration of a crowding agent (polyethylene glycol, PEG) to quantitatively assess relative solubility of proteins using about 200 µg of purified material. Our results demonstrate that this method is accurate and economical in material requirement and costs of reagents, which makes it suitable for high-throughput screening. This approach is freely-shared and based on a low cost, open-source liquid-handling robot. We anticipate that this method will facilitate the assessment of the developability of proteins and make it substantially more accessible.
Sponsorship
M.O. is a PhD student funded by AstraZeneca. P.S. is a Royal Society University Research Fellow (URF\R1\201461).
Funder references
Royal Society (URF\R1\201461)
Wellcome Trust (203249/Z/16/Z)
Identifiers
External DOI: https://doi.org/10.1038/s41598-021-01126-4
This record's URL: https://www.repository.cam.ac.uk/handle/1810/329647
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