Label-free target protein characterization for small molecule drugs: recent advances in methods and applications

Fu, Feng; Zhang, Weiyue; Chai, Yifeng; Guo, Dan; Chen, Xiaofei

doi:10.1016/j.jpba.2022.115107

Cited by 13 publications

(11 citation statements)

References 110 publications

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“…Therefore, the target protein can be easily identified by determining the binding-induced increase in proteolysis resistance. 42 Direct binding between geraniin and IL-1β can protect the latter from proteolysis by Pronase (Figure 1D). We determined the K D values of geraniin through its association with and dissociation from IL-1β or IL-1R immobilized on the CM5 sensor chip.…”

Section: Discussionmentioning

confidence: 99%

Geraniin Alleviates Inflammation in Caco-2 Cells and Dextran Sulfate Sodium-Induced Colitis Mice by Targeting IL-1β

Lee,

Jeong,

Park

et al. 2024

J. Agric. Food Chem.

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IL-1β is an important cytokine implicated in the progression of inflammatory bowel disease (IBD) and intestinal barrier dysfunction. The polyphenolic compound, geraniin, possesses bioactive properties, such as antitumor, antioxidant, antiinflammatory, antihypertensive, and antiviral activities; however, its IL-1β-targeted anticolitis activity remains unclear. Here, we evaluated the inhibitory effect of geraniin in IL-1β-stimulated Caco-2 cells and a dextran sulfate sodium (DSS)-induced colitis mouse model. Geraniin blocked the interaction between IL-1β and IL-1R by directly binding to IL-1β and inhibited the IL-1β activity. It suppressed IL-1β-induced intestinal tight junction damage in human Caco-2 cells by inhibiting IL-1β-mediated MAPK, NF-kB, and MLC activation. Moreover, geraniin administration effectively reduced colitis symptoms and attenuated intestinal barrier injury in mice by suppressing elevated intestinal permeability and restoring tight junction protein expression through the inhibition of MAPK, NF-kB, and MLC activation. Thus, geraniin exhibits anti-IL-1β activity and anticolitis effect by hindering the IL-1β and IL-1R interaction and may be a promising therapeutic anti-IL-1β agent for IBD treatment.

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Section: Discussionmentioning

confidence: 99%

Geraniin Alleviates Inflammation in Caco-2 Cells and Dextran Sulfate Sodium-Induced Colitis Mice by Targeting IL-1β

Lee,

Jeong,

Park

et al. 2024

J. Agric. Food Chem.

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“…66 Alternative chemoproteomic methods have been developed which circumvent the need for chemically modified probes. Proteomic strategies such as drug affinity responsive target stability (DARTS), 67 cellular thermal shift assay (CETSA), 68 thermal proteome profiling (TPP), 69,70 or limited proteolysis coupled with MS (LiP-MS) [71][72][73] employ native bioactive molecules to elucidate shifts in protein stability upon small molecule binding.…”

Section: Reviewmentioning

confidence: 99%

Monitoring host–pathogen interactions using chemical proteomics

Weigert Muñoz,

Zhao,

Sieber

2024

RSC Chem. Biol.

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“…Cellular thermal shift assay (CETSA), combined with mass spectrometry (also known as thermal proteome profiling (TPP) [ 41 ]), allows the study of PMIs in panoramic mode under conditions close to native ones, including directly in intact cells [ 42 , 43 ]. This method is based on the idea that binding to a metabolite can change the thermal stability of a protein.…”

Section: Strategies For Pmi Studiesmentioning

confidence: 99%

“…This method was recently applied to the screening of 896 B-Raf kinase inhibitors [ 48 ]. Thermal shift-based methods have an important limitation in that proteins with a melting temperature outside of the range of 40–75 °C (which is typical for most proteins) require more steps of temperature iteration for confident results, thus lowering the robustness of the method [ 43 ]. Moreover, it should be taken into account that not all interacting metabolites affect protein stability; therefore, CETSA, like other methods based on assessing the stability of molecular complexes, is prone to false negative results [ 49 ].…”

Section: Strategies For Pmi Studiesmentioning

confidence: 99%

The Knowns and Unknowns in Protein–Metabolite Interactions

Kurbatov

Dolgalev

Arzumanian

et al. 2023

IJMS

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Increasing attention has been focused on the study of protein–metabolite interactions (PMI), which play a key role in regulating protein functions and directing an orchestra of cellular processes. The investigation of PMIs is complicated by the fact that many such interactions are extremely short-lived, which requires very high resolution in order to detect them. As in the case of protein–protein interactions, protein–metabolite interactions are still not clearly defined. Existing assays for detecting protein–metabolite interactions have an additional limitation in the form of a limited capacity to identify interacting metabolites. Thus, although recent advances in mass spectrometry allow the routine identification and quantification of thousands of proteins and metabolites today, they still need to be improved to provide a complete inventory of biological molecules, as well as all interactions between them. Multiomic studies aimed at deciphering the implementation of genetic information often end with the analysis of changes in metabolic pathways, as they constitute one of the most informative phenotypic layers. In this approach, the quantity and quality of knowledge about PMIs become vital to establishing the full scope of crosstalk between the proteome and the metabolome in a biological object of interest. In this review, we analyze the current state of investigation into the detection and annotation of protein–metabolite interactions, describe the recent progress in developing associated research methods, and attempt to deconstruct the very term “interaction” to advance the field of interactomics further.

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Label-free target protein characterization for small molecule drugs: recent advances in methods and applications

Cited by 13 publications

References 110 publications

Geraniin Alleviates Inflammation in Caco-2 Cells and Dextran Sulfate Sodium-Induced Colitis Mice by Targeting IL-1β

Geraniin Alleviates Inflammation in Caco-2 Cells and Dextran Sulfate Sodium-Induced Colitis Mice by Targeting IL-1β

Monitoring host–pathogen interactions using chemical proteomics

The Knowns and Unknowns in Protein–Metabolite Interactions

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