Exploring the Functional Consequences of Protein Backbone Alteration in Ubiquitin through Native Chemical Ligation. (23rd August 2019)

• Record Type: Journal Article
• Authors: Werner, Halina M.; Estabrooks, Samuel K.; Preston, G. Michael; Brodsky, Jeffrey L.; Horne, W. Seth
• Is Part Of: Chembiochem. Volume 20:Number 18(2019)
• Page Start: 2346
• Page End: 2350
• Publication Date: 2019-08-23
• Subjects: foldamers -- heterogeneous backbones -- native chemical ligation -- protein mimetics -- ubiquitin; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201900225
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract: Ubiquitin (Ub) plays critical roles in myriad protein degradation and signaling networks in the cell. We report herein Ub mimetics based on backbones that blend natural and artificial amino acid units. The variants were prepared by a modular route based on native chemical ligation. Biological assays show that some are enzymatically polymerized onto protein substrates, and that the resulting Ub tags are recognized for downstream pathways. These results advance the size and complexity of folded proteins mimicked by artificial backbones and expand the functional scope of such agents. Abstract : A modular synthetic route based on native chemical ligation enables the systematic examination of folding and function in variants of the protein ubiquitin with altered chemical composition of the polypeptide backbone.