A chemical proteomics based enrichment technique targeting the interactome of the PDE5 inhibitor PF-4540124

Dadvar, Poupak; O’Flaherty, Martina; Scholten, Arjen; Rumpel, Klaus; Heck, Albert J. R.

doi:10.1039/b815709j

Cited by 27 publications

(36 citation statements)

References 33 publications

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“…Therefore, these affinity-based enrichment techniques, in combination with MS, have enabled the direct determination of protein-binding profiles of small molecule drugs under physiological conditions and represent one of the most direct approaches to screen for drug–protein interactions 79,80. The major drawback encountered in the affinity-based chemical proteomics is the presence in the pulled-down extract of nonspecifically bound proteins.…”

Section: Target Identification From Drug Action (Chemical Proteomics)mentioning

confidence: 99%

Advances in the proteomic discovery of novel therapeutic targets in cancer

Guo¹,

Zhang²,

Wang³

2013

DDDT

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Proteomic approaches are continuing to make headways in cancer research by helping to elucidate complex signaling networks that underlie tumorigenesis and disease progression. This review describes recent advances made in the proteomic discovery of drug targets for therapeutic development. A variety of technical and methodological advances are overviewed with a critical assessment of challenges and potentials. A number of potential drug targets, such as baculoviral inhibitor of apoptosis protein repeat-containing protein 6, macrophage inhibitory cytokine 1, phosphoglycerate mutase 1, prohibitin 1, fascin, and pyruvate kinase isozyme 2 were identified in the proteomic analysis of drug-resistant cancer cells, drug action, and differential disease state tissues. Future directions for proteomics-based target identification and validation to be more translation efficient are also discussed.

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Section: Target Identification From Drug Action (Chemical Proteomics)mentioning

confidence: 99%

Advances in the proteomic discovery of novel therapeutic targets in cancer

Guo¹,

Zhang²,

Wang³

2013

DDDT

View full text Add to dashboard Cite

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“…The recent developments in affinity-based enrichment techniques in combination with MS have enabled the direct determination of protein binding profiles of small molecule drugs under more physiological conditions. In this context, chemical proteomics represents one of the most direct approaches to screen for drug–protein interactions [38,39]. One possible strategy typically involves the immobilization of a (chemically modified) drug to a solid-state support (for example, beads), either directly or by using a flexible linker.…”

Section: Applying Chemical Proteomics To Biomarkers and Drug-targementioning

confidence: 99%

“…An example of the above-mentioned strategies which can be used to decrease the presence of non-specifically bound proteins is the recent identification of the interactome of the PDE5 inhibitors PF-4540124 [38], and PF-3717842 [43]. This approach shows how chemical proteomics might be used to profile the biochemical space (interactome) of small molecule inhibitors.…”

Section: Applying Chemical Proteomics To Biomarkers and Drug-targementioning

confidence: 99%

The Proteomics Big Challenge for Biomarkers and New Drug-Targets Discovery

Savino

Paduano

Preianò

et al. 2012

IJMS

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In the modern process of drug discovery, clinical, functional and chemical proteomics can converge and integrate synergies. Functional proteomics explores and elucidates the components of pathways and their interactions which, when deregulated, lead to a disease condition. This knowledge allows the design of strategies to target multiple pathways with combinations of pathway-specific drugs, which might increase chances of success and reduce the occurrence of drug resistance. Chemical proteomics, by analyzing the drug interactome, strongly contributes to accelerate the process of new druggable targets discovery. In the research area of clinical proteomics, proteome and peptidome mass spectrometry-profiling of human bodily fluid (plasma, serum, urine and so on), as well as of tissue and of cells, represents a promising tool for novel biomarker and eventually new druggable targets discovery. In the present review we provide a survey of current strategies of functional, chemical and clinical proteomics. Major issues will be presented for proteomic technologies used for the discovery of biomarkers for early disease diagnosis and identification of new drug targets.

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“…An example of a typical pull-down proteomics study involves the use of an immobilized inhibitor for phosphodiesterase 5 to study its interactome [65]. To gain specificity, selective precleaning and elution protocols were developed for efficient discrimination between specific and nonspecific or less-specific binding proteins.…”

Section: Introductionmentioning

confidence: 99%

Studying protein–protein affinity and immobilized ligand–protein affinity interactions using MS-based methods

Kool¹,

Jonker

Irth

et al. 2011

Anal Bioanal Chem

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This review discusses the most important current methods employing mass spectrometry (MS) analysis for the study of protein affinity interactions. The methods are discussed in depth with particular reference to MS-based approaches for analyzing protein–protein and protein–immobilized ligand interactions, analyzed either directly or indirectly. First, we introduce MS methods for the study of intact protein complexes in the gas phase. Next, pull-down methods for affinity-based analysis of protein–protein and protein–immobilized ligand interactions are discussed. Presently, this field of research is often called interactomics or interaction proteomics. A slightly different approach that will be discussed, chemical proteomics, allows one to analyze selectivity profiles of ligands for multiple drug targets and off-targets. Additionally, of particular interest is the use of surface plasmon resonance technologies coupled with MS for the study of protein interactions. The review addresses the principle of each of the methods with a focus on recent developments and the applicability to lead compound generation in drug discovery as well as the elucidation of protein interactions involved in cellular processes. The review focuses on the analysis of bioaffinity interactions of proteins with other proteins and with ligands, where the proteins are considered as the bioactives analyzed by MS.FigureApproach for analysis of protein complexes with MS

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A chemical proteomics based enrichment technique targeting the interactome of the PDE5 inhibitor PF-4540124

Cited by 27 publications

References 33 publications

Advances in the proteomic discovery of novel therapeutic targets in cancer

Advances in the proteomic discovery of novel therapeutic targets in cancer

The Proteomics Big Challenge for Biomarkers and New Drug-Targets Discovery

Studying protein–protein affinity and immobilized ligand–protein affinity interactions using MS-based methods

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