Department of Chemistry
ORCID IDs
http://orcid.org/0000-0002-3165-4539
Document Type
Article
Date of this Version
2020
Citation
ACS Omega 2020, 5, 12974−12978
Abstract
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.
Included in
Analytical Chemistry Commons, Medicinal-Pharmaceutical Chemistry Commons, Other Chemistry Commons
Comments
2020 American Chemical Society