STPP-UP: An alternative method for drug target identification using protein thermal stability

Zijlmans, Dick W.; Hernández-Quiles, Miguel; Jansen, Pascal W.T.C.; Becher, Isabelle; Stein, Frank; Savitski, Mikhail M.; Vermeulen, Michiel

doi:10.1016/j.jbc.2023.105279

Cited by 3 publications

(5 citation statements)

References 20 publications

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“…Another protocol is the single tube-TPP with uniform progression (STTPP-UP). Here, incremental heating of a single sample is applied, thereby saving time and material [126]. Generally, TPP is well suited for soluble proteins.…”

Section: Protein Stability-based Methodsmentioning

confidence: 99%

Investigating Antiprotozoal Chemotherapies with Novel Proteomic Tools—Chances and Limitations: A Critical Review

Müller,

Boubaker,

Müller

et al. 2024

IJMS

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Identification of drug targets and biochemical investigations on mechanisms of action are major issues in modern drug development. The present article is a critical review of the classical “one drug”—“one target” paradigm. In fact, novel methods for target deconvolution and for investigation of resistant strains based on protein mass spectrometry have shown that multiple gene products and adaptation mechanisms are involved in the responses of pathogens to xenobiotics rather than one single gene or gene product. Resistance to drugs may be linked to differential expression of other proteins than those interacting with the drug in protein binding studies and result in complex cell physiological adaptation. Consequently, the unraveling of mechanisms of action needs approaches beyond proteomics. This review is focused on protozoan pathogens. The conclusions can, however, be extended to chemotherapies against other pathogens or cancer.

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Section: Protein Stability-based Methodsmentioning

confidence: 99%

Investigating Antiprotozoal Chemotherapies with Novel Proteomic Tools—Chances and Limitations: A Critical Review

Müller,

Boubaker,

Müller

et al. 2024

IJMS

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“…1A ), insoluble protein is removed by ultracentrifugation (100 000 × g ) to improve signal-to-noise ratio (Ref. 21 ), or more recently with filter-aided benchtop centrifugation methods that increased throughput (Refs 37 , 38 ). Each temperature point in the vehicle and drug-treated conditions is labelled with a different isobaric TMT for precise and multiplexed relative quantification.…”

Section: Target Deconvolution Based On Thermal Denaturationmentioning

confidence: 99%

“…Alternatively, to increase throughput and decrease required starting material, a one-pot method named single-tube TPP with uniform progression (STPP-UP) was recently proposed, but did not perform as well as TPP in resolution, sensitivity or accuracy (Ref. 38 ). Rather than subjecting aliquots of a drug or vehicle-treated sample each to different temperatures as in TPP, a single sample per treatment condition is halved, one aliquot exposed to incrementally increasing temperature for equal exposure times.…”

Section: Target Deconvolution Based On Thermal Denaturationmentioning

confidence: 99%

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Stability-based approaches in chemoproteomics

George,

Dueñas,

Marín-Rubio

et al. 2024

Expert Rev. Mol. Med.

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Target deconvolution can help understand how compounds exert therapeutic effects and can accelerate drug discovery by helping optimise safety and efficacy, revealing mechanisms of action, anticipate off-target effects and identifying opportunities for therapeutic expansion. Chemoproteomics, a combination of chemical biology with mass spectrometry has transformed target deconvolution. This review discusses modification-free chemoproteomic approaches that leverage the change in protein thermodynamics induced by small molecule ligand binding. Unlike modification-based methods relying on enriching specific protein targets, these approaches offer proteome-wide evaluations, driven by advancements in mass spectrometry sensitivity, increasing proteome coverage and quantitation methods. Advances in methods based on denaturation/precipitation by thermal or chemical denaturation, or by protease degradation are evaluated, emphasising the evolving landscape of chemoproteomics and its potential impact on future drug-development strategies.

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“…Another protocol is the single tube-TPP with uniform progression (STTPP-UP). Here, incrementally heating of a single sample is applied thereby saving time and material [118]. Generally, TPP is well suited for soluble proteins.…”

Section: Thermal Proteome Profilingmentioning

confidence: 99%

Investigating Antiprotozoal Chemotherapies with Novel Proteomic Tools – Chances and Limitations. A Critical Review

Müller,

Boubaker,

Müller

et al. 2024

Preprint

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Identification of drug targets and biochemical investigations on mechanisms of action is a are major issues in modern drug development. The present article reviews the classical “one drug” – “one target” paradigm. Novel methods for target deconvolution and for investigation of resistant strains based on protein mass spectrometry have shown that multiple gene products and adapta-tion mechanisms are involved in responses of pathogens to xenobiotics. This review is focused on protozoan pathogens. The conclusions can, however, be extended to chemotherapies against other pathogens or cancer. For this review we have searched Pubmed (pubmed.ncbi.nlm.nih.gov) and Web of Science (webofscience.com) using the key words listed below (status May 2024)

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STPP-UP: An alternative method for drug target identification using protein thermal stability

Cited by 3 publications

References 20 publications

Investigating Antiprotozoal Chemotherapies with Novel Proteomic Tools—Chances and Limitations: A Critical Review

Investigating Antiprotozoal Chemotherapies with Novel Proteomic Tools—Chances and Limitations: A Critical Review

Stability-based approaches in chemoproteomics

Investigating Antiprotozoal Chemotherapies with Novel Proteomic Tools – Chances and Limitations. A Critical Review

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