Analysis of Biologics Molecular Descriptors towards Predictive Modelling for Protein Drug Development Using Time-Gated Raman Spectroscopy

Jaakko Itkonen, Leo Ghemtio, Daniela Pellegrino, Pia J. Jokela, Henri Xhaard, Marco G. Casteleijn*

*Corresponding author for this work

    Research output: Contribution to journalArticleScientificpeer-review

    5 Citations (Scopus)

    Abstract

    Pharmaceutical proteins, compared to small molecular weight drugs, are relatively fragile molecules, thus necessitating monitoring protein unfolding and aggregation during production and post-marketing. Currently, many analytical techniques take offline measurements, which cannot directly assess protein folding during production and unfolding during processing and storage. In addition, several orthogonal techniques are needed during production and market surveillance. In this study, we introduce the use of time-gated Raman spectroscopy to identify molecular descriptors of protein unfolding. Raman spectroscopy can measure the unfolding of proteins in-line and in real-time without labels. Using K-means clustering and PCA analysis, we could correlate local unfolding events with traditional analytical methods. This is the first step toward predictive modeling of unfolding events of proteins during production and storage.

    Original languageEnglish
    Article number1639
    Number of pages18
    JournalPharmaceutics
    Volume14
    Issue number8
    DOIs
    Publication statusPublished - Aug 2022
    MoE publication typeA1 Journal article-refereed

    Funding

    This research was funded by the Academy of Finland project 303884 and VTT technical research Centre of Finland. L.G. gratefully acknowledges the support of the Drug Discovery and Chemical Biology Network of Finland. J.I. has also been funded by grants from the Finnish Cultural Foundation, the Evald and Hilda Nissi Foundation, the Päivikki and Sakari Sohlberg Foundation, and the Paulo Foundation. D.P. received Erasmus+ program funding from the Italian Ministry of Education.

    Keywords

    • biologics
    • CD
    • DLS
    • in-line measurement
    • K-means clustering
    • PCA
    • pharmaceutical proteins
    • protein unfolding
    • Raman spectroscopy
    • tryptophan fluorescence

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