Projects per year
Abstract
Quantitative drug imaging in live cells is a major challenge in drug discovery and development. Many drug screening techniques are performed in solution, and therefore do not consider the impact of the complex cellular environment in their result. As such, important features of drug-cell interactions may be overlooked. In this study, Raman microscopy is used as a powerful technique for semi-quantitative imaging of Strathclyde-minor groove binders (S-MGBs) in mammalian cells under biocompatible imaging conditions. Raman imaging determined the influence of the tail group of two novel minor groove binders (S-MGB-528 and S-MGB-529) in mammalian cell models. These novel S-MGBs contained alkyne moieties which enabled analysis in the cell-silent region of the Raman spectrum. The intracellular uptake concentration, distribution and mechanism were evaluated as a function of the pKa of the tail group, morpholine and amidine, for S-MGB-528 and S-MGB-529, respectively. Although S-MGB-529 had a higher binding affinity to the minor groove of DNA in solution-phase measurements, the Raman imaging data indicated that S-MGB-528 showed a greater degree of intracellular accumulation. Furthermore, using high resolution stimulated Raman scattering (SRS) microscopy, the initial localisation of S-MGB-528 was shown to be in the nucleus before accumulation in the lysosome, which was demonstrated using a multimodal imaging approach. This study highlights the potential of Raman spectroscopy for semi-quantitative drug imaging studies and highlights the importance of imaging techniques to investigate drug-cell interactions, to better inform the drug design process.
Original language | English |
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Pages (from-to) | 1403-1415 |
Number of pages | 13 |
Journal | RSC Chemical Biology |
Volume | 3 |
Issue number | 12 |
Early online date | 26 Sept 2022 |
DOIs | |
Publication status | Published - 26 Sept 2022 |
Keywords
- drug imaging
- drug discovery
- chemical biology
- Raman microscopy
- minor groove binders (MGBs)
- Raman spectroscopy
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Dive into the research topics of 'Ratiometric imaging of minor groove binders in mammalian cells using Raman microscopy'. Together they form a unique fingerprint.Projects
- 7 Finished
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Doctoral Training Partnership 2020-2021 University of Strathclyde | Tyson-Hirst, Izaak
Beveridge, R. (Principal Investigator), Burley, G. (Co-investigator) & Tyson-Hirst, I. (Research Co-investigator)
EPSRC (Engineering and Physical Sciences Research Council)
1/01/21 → 14/04/25
Project: Research Studentship - Internally Allocated
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FFL Understanding intrinsically disordered proteins and their potential as new drug targets through novel measurement capabilities
Beveridge, R. (Fellow)
MRC (Medical Research Council)
1/11/20 → 31/10/24
Project: Research
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Investigating a novel class of Gram-negative active antibiotic suitable for clinical use
Scott, F. (Principal Investigator), Hunter, I. (Co-investigator), Suckling, C. (Co-investigator) & Tucker, N. (Co-investigator)
1/11/20 → 30/04/23
Project: Research
Datasets
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Data for: "Ratiometric imaging of minor groove binders in mammalian cells using Raman microscopy"
Tentellino, C. (Creator), Tipping, W. (Contributor), McGee, L. (Contributor), Bain, L. (Contributor), Wetherill, C. (Contributor), Laing, S. (Contributor), Tyson-Hirst, I. (Contributor), Suckling, C. (Contributor), Beveridge, R. (Contributor), Scott, F. (Contributor), Faulds, K. (Contributor) & Graham, D. (Contributor), University of Strathclyde, 7 Oct 2022
DOI: 10.15129/4b0dbf49-377c-4642-b95d-0ac8ef2e11c6
Dataset