S30: Protein farnesyltransferase: A useful enzyme for the preparation of site-specific protein conjugates

Site-specific chemical modification of proteins is important for many applications in biology and biotechnology. Our laboratory and others have exploited the high specificity of the enzyme protein farnesyltransferase (PFTase) to site-specifically modify proteins through the use of alternative substrates that incorporate bioorthogonal functionality including azides, alkynes and aldehydes. Fluorophores have also been directly incorporated using this approach. Given the specificity of the PFTase-catalyzed reaction coupled with the ability to introduce a CAAX-box recognition sequence onto almost any protein, this method constitutes a general approach for selective modification of recombinant proteins. This presentation will focus on recent advances using the PFTase technique for protein labeling including the preparation of mutant PFTase variants with altered substrate specificity and applications of the PFTase strategy for site-specific protein PEGylation for therapeutic applications.