Mass Spectrometry Detection and Imaging of a Non-Covalent Protein-Drug Complex in Tissue from Orally Dosed Rats

Eva Illes-Toth; Oliver J Hale; James W Hughes; Nicole Strittmatter; Jonathan Rose; Ben Clayton; Rebecca Sargeant; Stewart Jones; Andreas Dannhorn; Richard J A Goodwin; Helen J Cooper

doi:10.1002/anie.202202075

Mass Spectrometry Detection and Imaging of a Non-Covalent Protein-Drug Complex in Tissue from Orally Dosed Rats

Eva Illes-Toth, Oliver J Hale, James W Hughes, Nicole Strittmatter, Jonathan Rose, Ben Clayton, Rebecca Sargeant, Stewart Jones, Andreas Dannhorn, Richard J A Goodwin, Helen J Cooper

Biosciences

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Abstract

Here, we demonstrate detection by mass spectrometry of an intact protein-drug complex directly from liver tissue from rats that had been orally dosed with the drug. The protein-drug complex comprised fatty acid binding protein 1, FABP1, non-covalently bound to the small molecule therapeutic bezafibrate. Moreover, we demonstrate spatial mapping of the [FABP1+bezafibrate] complex across a thin section of liver by targeted mass spectrometry imaging. This work is the first demonstration of in situ mass spectrometry analysis of a non-covalent protein-drug complex formed in vivo and has implications for early stage drug discovery by providing a route to target-drug characterization directly from the physiological environment.

Original language	English
Article number	e202202075
Journal	Angewandte Chemie (International Edition)
Volume	61
Issue number	36
Early online date	13 Jul 2022
DOIs	https://doi.org/10.1002/anie.202202075
Publication status	E-pub ahead of print - 13 Jul 2022

Bibliographical note

Keywords

Ex vivo Tissue
Mass Spectrometry Imaging
Native Ambient Mass Spectrometry
Protein–Drug Complex

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10.1002/anie.202202075Licence: Creative Commons: Attribution (CC BY)

Angew Chem Int Ed - 2022 - Illes‐Toth - Mass Spectrometry Detection and Imaging of a Non‐Covalent Protein Drug Complex inFinal published version, 3.27 MBLicence: Creative Commons: Attribution (CC BY)

A new mass spectrometer for structural proteomics and protein imaging
Thomas, C. (Co-Investigator), Grant, M. (Co-Investigator), Lovering, A. (Co-Investigator), Alderwick, L. (Co-Investigator), Tomlinson, M. (Co-Investigator), Winn, P. (Co-Investigator), Knowles, T. (Co-Investigator), Cooper, H. (Principal Investigator), Styles, I. (Co-Investigator), Gibbs, D. (Co-Investigator), Huber, D. (Co-Investigator), Bhatt, A. (Co-Investigator) & Leney, A. (Co-Investigator)
Biotechnology & Biological Sciences Research Council
1/07/19 → 30/06/20
Project: Research
NAMS: Native ambient mass spectrometry
Cooper, H. (Principal Investigator)
Engineering & Physical Science Research Council
1/06/19 → 30/11/23
Project: Research
A new tool to support drug discovery: Native LESA mass spectrometry (NESA)
Alderwick, L. (Co-Investigator) & Cooper, H. (Principal Investigator)
Engineering & Physical Science Research Council
1/04/18 → 31/03/21
Project: Research Councils

Data to accompany "Mass Spectrometry Detection and Imaging of a Non-Covalent Protein-Drug Complex in Tissue from Orally-Dosed Rats"
Cooper, H. (Creator), University of Birmingham, 30 May 2022
DOI: 10.25500/edata.bham.00000845
Dataset

Cite this

Illes-Toth, E., Hale, O. J., Hughes, J. W., Strittmatter, N., Rose, J., Clayton, B., Sargeant, R., Jones, S., Dannhorn, A., Goodwin, R. J. A., & Cooper, H. J. (2022). Mass Spectrometry Detection and Imaging of a Non-Covalent Protein-Drug Complex in Tissue from Orally Dosed Rats. Angewandte Chemie (International Edition) , 61(36), Article e202202075. Advance online publication. https://doi.org/10.1002/anie.202202075

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abstract = "Here, we demonstrate detection by mass spectrometry of an intact protein-drug complex directly from liver tissue from rats that had been orally dosed with the drug. The protein-drug complex comprised fatty acid binding protein 1, FABP1, non-covalently bound to the small molecule therapeutic bezafibrate. Moreover, we demonstrate spatial mapping of the [FABP1+bezafibrate] complex across a thin section of liver by targeted mass spectrometry imaging. This work is the first demonstration of in situ mass spectrometry analysis of a non-covalent protein-drug complex formed in vivo and has implications for early stage drug discovery by providing a route to target-drug characterization directly from the physiological environment.",

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AU - Rose, Jonathan

AU - Clayton, Ben

AU - Sargeant, Rebecca

AU - Jones, Stewart

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Mass Spectrometry Detection and Imaging of a Non-Covalent Protein-Drug Complex in Tissue from Orally Dosed Rats

Abstract

Bibliographical note

Keywords

Access to Document

Fingerprint

Projects

A new mass spectrometer for structural proteomics and protein imaging

NAMS: Native ambient mass spectrometry

A new tool to support drug discovery: Native LESA mass spectrometry (NESA)

Datasets

Data to accompany "Mass Spectrometry Detection and Imaging of a Non-Covalent Protein-Drug Complex in Tissue from Orally-Dosed Rats"

Cite this