Targeting the Intrinsically Disordered Proteome Using Small-Molecule Ligands.
Methods Enzymol
; 611: 703-734, 2018.
Article
em En
| MEDLINE
| ID: mdl-30471705
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Espectrometria de Fluorescência
/
Ressonância Magnética Nuclear Biomolecular
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Proteínas Intrinsicamente Desordenadas
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article