Palladium-Assisted Cleavage of Peptides and Proteins Containing a Backbone with Thiazolidine Linkage

Muhammad Jbara, Shay Laps, Suman Kumar Maity, Ashraf Brik

Research output: Contribution to journalArticlepeer-review

Abstract

The design and synthesis of biomolecules that are responsive to external stimuli is of great interest in various research areas, such as in the preparation of smart biomaterial and chemical biology. Polypeptide backbone disassembly as a response to a particular stimulus is of interest, as it leads to a complete loss of the protein tertiary structure and, as a result, to a loss of function. In this study, a strategy based on palladium-assisted efficient cleavage of backbone thiazolidine linkage in peptides and proteins was developed. Using a fluorescence-based assay, encompassing ubiquitinated peptide with a quenching florescence pair, it was possible to optimize the cleavage step after rapid screening of various conditions, such as the type of metal complexes and reaction additives. The optimized conditions prompted fast cleavage of the thiazolidine linkage. The straightforward introduction of a backbone thiazolidine linkage in peptide and proteins coupled with the chemical methods used offers new opportunities in controlling macromolecule function and might, with the aid of cellular protein delivery methods, be applied in cellular settings.

Original languageEnglish
Pages (from-to)14851-14855
Number of pages5
JournalChemistry - A European Journal
Volume22
Issue number42
DOIs
StatePublished - 10 Oct 2016
Externally publishedYes

Keywords

  • chemical protein synthesis
  • cleavable linker
  • palladium
  • polypeptide cleavage
  • thiazolidine linkage

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