A Luminescence-Based System for Identification of Genetically Encodable Inhibitors of Protein Aggregation.
Journal
ACS omega
ISSN: 2470-1343
Titre abrégé: ACS Omega
Pays: United States
ID NLM: 101691658
Informations de publication
Date de publication:
09 Jun 2020
09 Jun 2020
Historique:
received:
21
02
2020
accepted:
15
05
2020
entrez:
18
6
2020
pubmed:
18
6
2020
medline:
18
6
2020
Statut:
epublish
Résumé
Molecules that disrupt protein aggregation represent potential tool compounds for the investigation of numerous human disease states. However, the identification of small molecules capable of disrupting protein aggregation has proven challenging. Larger biomolecules such as antibodies and proteins are promising alternatives due to their increased size. Despite the promise of protein-based inhibitors, generalizable assays are needed to more readily identify proteins capable of inhibiting aggregation. Herein, we utilize our previously reported self-assembling NanoLuc luciferase fragments to engineer a platform in which both detection reagents are expressed from the same plasmid, enabling facile co-transformation with a genetically encodable inhibitor. This streamlined system is capable of detecting changes in the solubility of amylin, huntingtin, and amyloid-β (Aβ) proteins in response to mutations, small-molecule inhibitors, and expression of genetically encodable inhibitors. This improved platform provides a means to begin to identify protein-based inhibitors with improved efficacy.
Identifiants
pubmed: 32548481
doi: 10.1021/acsomega.0c00779
pmc: PMC7288563
doi:
Types de publication
Journal Article
Langues
eng
Pagination
12974-12978Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM119751
Pays : United States
Informations de copyright
Copyright © 2020 American Chemical Society.
Déclaration de conflit d'intérêts
The authors declare no competing financial interest.
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