Keynote
Palladium in Peptide/Protein Synthesis and Modification

In this talk, I will present our recent synthetic approaches applying palladium chemistry for facilitating protein synthesis and modification. Using these approaches, various synthetic protein targets in particular ubiquitinated proteins will be presented. The enzymatic attachment of ubiquitin to a specific protein target is a widely utilized posttranslational modification in cellular functions and has been implicated in several diseases. The majority of biochemical, biophysical and structural studies in the field rely on the in vitro enzymatic reconstitution of this complex modification for the protein of interest. However, the enzymatic approaches are often challenged by difficulties in obtaining ubiquitinated conjugates in acceptable homogeneity and workable quantities. Our group has been developing novel chemical approaches for the efficient and site-specific protein ubiquitination to overcome these limitations. In these syntheses, the utility of palladium for the rapid removal of various protecting groups essential in the ligation process of unprotected peptides was demonstrated. Moreover, we extended the use of palladium chemistry for the removal of solubilizing tags, which are used to aid the solubility and handling of difficult peptides. Finally, the use of palladium for the cleavage of peptides and proteins containing a thiazolidine linkage will also be discussed.