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Exploring the Functional Consequences of Protein Backbone Alteration in Ubiquitin through Native Chemical Ligation.


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.

SUBMITTER: Werner HM 

PROVIDER: S-EPMC6752966 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Exploring the Functional Consequences of Protein Backbone Alteration in Ubiquitin through Native Chemical Ligation.

Werner Halina M HM   Estabrooks Samuel K SK   Preston G Michael GM   Brodsky Jeffrey L JL   Horne W Seth WS  

Chembiochem : a European journal of chemical biology 20190823 18


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 pr  ...[more]

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