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)

Research output: Contribution to journalArticleScientificpeer-review

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

Keywords

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

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