In recent years, ubiquitylation has come to the forefront of research involving post-translational modifications of proteins in eukaryotic cell systems. In this process the lysine side chain of a target protein is modified by ubiquitin, a 76 residue globular protein. Ubiquitylation of proteins is a reversible process that can lead to the alteration of protein structure, activity, stability, and intracellular localization, resulting in a diverse array of biological consequences. The E1, E2, and E3 enzymes attach ubiquitin to protein substrates while deubiquitylating enzymes remove ubiquitin from proteins. To understand the complexities of ubiquitin signaling both in vitro and in vivo, it is imperative to produce ubiquitin polymers with high homology to those found in the cell; even more important is the stability and versatility of the ubiquitin polymers. Since native ubiquitin chains are targeted by intracellular machinery out of the control of the experimenter, we have developed a method to produce non-hydrolyzable ubiquitin polymers that can be utilized in a diverse array of enzyme assays. The synthesis of these unique polymers involves the use of thiol-ene chemistry to produce ubiquitin chains that closely mimic endogenous ubiquitin products while being able to withstand degradation. Thiol-ene chemistry is classified as a type of �click� chemistry in which a thioether linkage can be forged via the free-radical reaction between a double bond functionality and a thiol group.

Synthesis of non-hydrolyzable ubiquitin polymers using thiol-ene chemistry

247th National Meeting (2014)

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