The Development of a Fluorescence-Based Competitive Assay Enabled the Discovery of Dimeric Cyclic Peptide Modulators of Ubiquitin Chains.

ABSTRACT: Development of modulators targeting specific interactions of ubiquitin-based conjugates with their partners is a formidable task since it requires a suitable screening assay and homogeneous ubiquitin conjugates. We developed a novel high-throughput strategy for screening ligands for Lys48-linked tetraubiquitin chain in a relatively simple, fast, and affordable manner. This approach combined with a state-of-the-art toolbox of chemical protein synthesis and a specially optimized Cys deprotection protocol enabled us to design highly potent, Lys48-linked tetraubiquitin chain selective "next generation" dimeric peptide modulators. The dimeric peptide exhibited cancer cell permeability and induced cell death with higher efficiency compared to its monocyclic analogue. These features make our dime

SUBMITTER: Vamisetti GB 

PROVIDER: S-EPMC8048552 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature