Differential scanning fluorimetry (DSF) screen to identify inhibitors of Hsp60 protein–protein interactions. Issue 22 (27th May 2020)

• Record Type: Journal Article
• Authors: Shao, Hao; Oltion, Keely; Wu, Taia; Gestwicki, Jason E.
• Is Part Of: Organic & biomolecular chemistry. Volume 18:Issue 22(2020)
• Page Start: 4157
• Page End: 4163
• Publication Date: 2020-05-27
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/d0ob00928h
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : Homo-oligomers are difficult drug targets. Here, Differential Scanning Fluorimetry (DSF) is introduced as a method to identify inhibitors of these systems, by discriminating between oligomers and monomers based on their thermal stability. Abstract : There are relatively few methods available for discovering inhibitors of the protein–protein interactions (PPIs) that hold together homo-oligomers. We envisioned that Differential Scanning Fluorimetry (DSF) might be a versatile way to discover this type of inhibitor because oligomers are often more thermally stable than monomers. Using the homo-heptameric chaperonin, Hsp60, as a model, we screened ∼5000 diverse compounds in 384-well plates by DSF, revealing molecules that partially inhibited oligomerization. Because DSF does not require protein labeling or structural information, we propose that it could be a versatile way to uncover PPI inhibitors.