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Targeting the intrinsically disordered proteome using small-molecule ligands

Item Type:Review
Title:Targeting the intrinsically disordered proteome using small-molecule ligands
Creators Name:Wójcik, S. and Birol, M. and Rhoades, E. and Miranker, A.D. and Levine, Z.A.
Abstract:Intrinsically disordered proteins (IDPs) and regions (IDRs) make up a significant part of the proteome and facilitate a wide range of physiological and pathological functions that are only beginning to be understood. As such, they are highly attractive targets for drug development and bioengineering. However, their inability to adopt well-defined structures provides significant obstacles for developing ligands that regulate their behaviors. In this chapter, we review how the conformational flexibility of IDPs and their propensity to phase separate make them tractable targets for small-molecule manipulation. We also describe both theoretical and experimental approaches to characterize disordered proteins, including novel thermodynamic and single-molecule techniques that help identify complimentary partners of IDPs and their ability to shift protein ensembles toward preferred conformations.
Keywords:Intrinsically Disordered Proteins, Small-Molecule Design, Drug Design, Protein Disorder, Coacervation, Protein Aggregation, Animals
Source:Methods in Enzymology
Publisher:Academic Press
Page Range:703-734
Official Publication:https://doi.org/10.1016/bs.mie.2018.09.036
PubMed:View item in PubMed

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