Monitoring protein communities and their responses to therapeutics.

Nature Reviews. Drug Discovery
Hanna G Budayeva, Donald S Kirkpatrick

Abstract

Most therapeutics are designed to alter the activities of proteins. From metabolic enzymes to cell surface receptors, connecting the function of a protein to a cellular phenotype, to the activity of a drug and to a clinical outcome represents key mechanistic milestones during drug development. Yet, even for therapeutics with exquisite specificity, the sequence of events following target engagement can be complex. Interconnected communities of structural, metabolic and signalling proteins modulate diverse downstream effects that manifest as interindividual differences in efficacy, adverse effects and resistance to therapy. Recent advances in mass spectrometry proteomics have made it possible to decipher these complex relationships and to understand how factors such as genotype, cell type, local environment and external perturbations influence them. In this Review, we explore how proteomic technologies are expanding our understanding of protein communities and their responses to large- and small-molecule therapeutics.

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Citations

Mar 12, 2021·Wiley Interdisciplinary Reviews. RNA·J J David HoPhilip A Marsden
Mar 23, 2021·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Nathan P McMahonSummer L Gibbs
Jun 16, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Bin ZhangXiaobo Sun
Aug 6, 2021·Proceedings of the National Academy of Sciences of the United States of America·Andrew WheatLan Huang

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Methods Mentioned

BETA
acetylation
pull-down
affinity purification
nuclear translocation
chemoproteomic
proteome-profiling
proteomic profiling
xenograft
immunoprecipitation

Software Mentioned

BioID
Split
LOPIT
- BioID
Virotrap

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