Mass Spectrometry Detection and Imaging of a Non-Covalent Protein-Drug Complex in Tissue from Orally Dosed Rats.
Angew Chem Weinheim Bergstr Ger
; 134(36): e202202075, 2022 Sep 05.
Article
em En
| MEDLINE
| ID: mdl-38505542
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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MEDLINE
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En
Ano de publicação:
2022
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Article