Techniques used to study protein–small molecule interactions
Chemoproteomics (also known as chemical proteomics) entails a broad array of techniques used to identify and interrogate protein-small molecule interactions.[1] Chemoproteomics complements phenotypic drug discovery, a paradigm that aims to discover lead compounds on the basis of alleviating a disease phenotype, as opposed to target-based drug discovery (reverse pharmacology), in which lead compounds are designed to interact with predetermined disease-driving biological targets.[2] As phenotypic drug discovery assays do not provide confirmation of a compound's mechanism of action, chemoproteomics provides valuable follow-up strategies to narrow down potential targets and eventually validate a molecule's mechanism of action.[2] Chemoproteomics also attempts to address the inherent challenge of drug promiscuity in small molecule drug discovery by analyzing protein-small molecule interactions on a proteome-wide scale. A major goal of chemoproteomics is to characterize the interactome of drug candidates to gain insight into mechanisms of off-target toxicity and polypharmacology.[3]
Chemoproteomics assays can be stratified into three basic types. Solution-based approaches involve the use of drug analogs that chemically modify target proteins in solution, tagging them for identification. Immobilization-based approaches seek to isolate potential targets or ligands by anchoring their binding partners to an immobile support. Derivatization-free approaches aim to infer drug-target interactions by observing changes in protein stability or drug chromatography upon binding. Computational techniques complement the chemoproteomic toolkit as parallel lines of evidence supporting potential drug-target pairs, and are used to generate structural models that inform lead optimization. Several targets of high profile drugs have been identified using chemoproteomics, and the continued improvement of mass spectrometer sensitivity and chemical probe technology indicates that chemoproteomics will play a large role in future drug discovery.
^Wang, Lei (2020-08-21). "Chemical Tools and Mass Spectrometry-based Approaches for Exploring Reactivity and Selectivity of Small Molecules in Complex Proteomes". Doctoral Dissertations.
using chemoproteomics, and the continued improvement of mass spectrometer sensitivity and chemical probe technology indicates that chemoproteomics will...
chemical compounds against biological targets using biochemical or chemoproteomics assays, where the compounds may be from novel synthetic chemical libraries...
the compounds through target validation experiments often involving chemoproteomics. More recently it has become popular to develop a hypothesis that a...
therapeutic effect. Omics based methods use omics technologies, such as chemoproteomics, reverse genetics and genomics, transcriptomics, and proteomics, to...
Isoxazole as a Native Photo-Cross-Linker for Photoaffinity Labeling and Chemoproteomics". Angew. Chem. Int. Ed. 61 (47): e202209947. doi:10.1002/anie.202209947...
at the use of tool compounds from a systems perspective. The use of chemoproteomics offers strategies to develop a more holistic understanding of the proteome-wide...
heavily benefited from advances in human genomics, network biology, and chemoproteomics. It is now possible to identify serious repurposing candidates by finding...
CEllular Thermal Shift Assay (CETSA®) is a patented label free chemoproteomics method that has enabled measurements of compound target engagement in intact...
as target deconvolution) and validation, often through the use of chemoproteomics, to identify the mechanisms through which a phenotypic hit works. Phenotypic...
activity, these particular chemicals are registered and analysed. Chemoproteomics is a field of study that incorporates the use of chemical libraries...
their structures and functions. Mass spectrometry techniques are used. Chemoproteomics: An array of techniques used to study protein-small molecule interactions...
Photoaffinity labeling is a chemoproteomics technique used to attach "labels" to the active site of a large molecule, especially a protein. The "label"...
chemical libraries is used to identify drug targets (forward genetics or chemoproteomics) or to validate those targets in experimental models of disease (reverse...
Clark Lambert, W. (1 March 2007). "Cell biology, chemogenomics and chemoproteomics – application to drug discovery". Expert Opinion on Drug Discovery...
deconvolution experiments to ascertain. The growth of the field of chemoproteomics has provided numerous strategies to identify drug targets in these...
clinical proteomics studies. The Kessler Lab is currently developing chemoproteomics methods to profile active ubiquitin processing enzymes, in particular...
defensive response of plants to herbivory. A branch of proteomics called chemoproteomics provides numerous tools and techniques to detect protein targets of...
Isoxazole as a Native Photo-Cross-Linker for Photoaffinity Labeling and Chemoproteomics". Angew. Chem. Int. Ed. 61 (47): e202209947. doi:10.1002/anie.202209947...
Affinity chromatography is part of a larger suite of techniques used in chemoproteomics based drug target identification. The WAC technology is demonstrated...
but there has been some progress (by 2009) targeting these sites. Chemoproteomics techniques have recently expanded the scope of what is deemed a druggable...
biological conditions: the concept of a "click" reaction has been used in chemoproteomic, pharmacological, biomimetic and molecular machinery applications. However...
example, offers a fourth-year course in synthetic chemical biology. Chemoproteomics Chemical genetics Chemogenomics Schreiber SL (July 2005). "Small molecules:...
Science. Fatty acid amide hydrolase Activity-based protein profiling Chemoproteomics Viegas, Jennifer (2 February 2016). "Profile of Benjamin Cravatt"....
Savitski MM, Dittmann A, Grandi P, Michon AM, et al. (March 2011). "Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes"...
functional map of a cell's processes, drug target identification using chemoproteomics, and to predict the function of uncharacterized genes. In 2010, the...
recently, drug-small molecule interactions, a field of study called chemoproteomics. Thus, it has shown great promise in monitoring side-effects of small...
cause psychedelic effects at high doses. The growth of the field of chemoproteomics has offered a variety of strategies to identify off-targets on a proteome...
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