Mass Spectrometry Detection and Imaging of a Non-Covalent Protein-Drug Complex in Tissue from Orally Dosed Rats.
Mass Spectrometry Detection and Imaging of a Non-Covalent Protein-Drug Complex in Tissue from Orally Dosed Rats.
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DOI：
10.1002/anie.202202075
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发表时间：
2022-09-05
影响因子：
16.6
通讯作者：
Cooper, Helen J.
中科院分区：
文献类型：
--
作者：
Illes-Toth, Eva;Hale, Oliver J.;Hughes, James W.;Strittmatter, Nicole;Rose, Jonathan;Clayton, Ben;Sargeant, Rebecca;Jones, Stewart;Dannhorn, Andreas;Goodwin, Richard J. A.;Cooper, Helen J.
在这里，我们展示了通过质谱法直接从口服药物的大鼠的肝组织中检测完整的蛋白质-药物复合物。该蛋白-药物复合物由脂肪酸结合蛋白1 （FABP1）组成，该蛋白与小分子治疗药物贝扎布酸非共价结合。此外，我们通过靶向质谱成像证明了[FABP1+ bezafbrate]复合物在肝脏薄片上的空间映射。这项工作首次证明了在体内形成的非共价蛋白质-药物复合物的原位质谱分析，并通过提供直接从生理环境中进行靶药物表征的途径，对早期药物发现具有重要意义。采用天然环境质谱法在口服给药大鼠离体肝组织中检测内源性肝脂肪酸结合蛋白（FABP1）与小分子治疗药物贝扎菲特在体内形成的完整蛋白-药物复合物。利用纳米喷雾解吸电喷雾电离技术对蛋白质-药物复合物的空间分布进行了成像。
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. The intact protein–drug complex formed in vivo between endogenous liver fatty acid binding protein (FABP1) and the small molecule therapeutic bezafibrate was detected in ex vivo liver tissue from orally dosed rats by native ambient mass spectrometry. The spatial distribution of the protein–drug complex was imaged by nanospray desorption electrospray ionization.
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影响因子：
7.4
作者：
Hale OJ;Cooper HJ
通讯作者：
Cooper HJ
影响因子：
4.2
作者：
Roach, Patrick J.;Laskin, Julia;Laskin, Alexander
通讯作者：
Laskin, Alexander
DOI：
10.1016/0005-2760(95)00170-0
发表时间：
1995-12-07
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM
影响因子：
--
作者：
Rolf, B;OudenampsenKruger, E;Spener, F
通讯作者：
Spener, F
影响因子：
15
作者：
Sisley, Emma K.;Hale, Oliver J.;Cooper, Helen J.
通讯作者：
Cooper, Helen J.
影响因子：
4.8
作者：
Thompson, J;Winter, N;Banaszak, L
通讯作者：
Banaszak, L