Non-enzymatic synthesis of ubiquitin chains: Where chemistry makes a difference

Hosahalli P. Hemantha, Ashraf Brik

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Ubiquitination is a highly important posttranslational modification in eukaryotic cells where a target protein is conjugated to ubiquitin or a chain of ubiquitins via an isopeptide bond to trigger various cellular events such as proteasomal degradation. Rigorous investigations of the ubiquitin signal at the molecular level require homogeneous samples of ubiquitin chains in their free form or as anchored to a protein substrate in adequate quantities. The complexity of ubiquitin chains in terms of linkage types (owing to presence of seven Lys in ubiquitin) makes them difficult to prepare via enzymatic methods. Even more challenging is the attachment of these chains to a protein target at a selected site. This dearth is being filled by the recent developments of novel chemical tools that offer atomic level control over the synthesis for structural and functional studies. These emerging chemical approaches are discussed in this mini-review with focus on the preparation of ubiquitin chains to aid the ongoing efforts in understanding their role in the ubiquitin signal.

Original languageEnglish
Pages (from-to)3411-3420
Number of pages10
JournalBioorganic and Medicinal Chemistry
Issue number12
StatePublished - 15 Jun 2013


  • Isopeptide bond
  • Protein synthesis
  • Ubiquitin
  • Ubiquitin chains
  • Ubiquitination

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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