Protein farnesyltransferase has been shown to transfer a large variety of non-natural hydrophobic isoprenoid containing substrates onto proteins and peptides ending in a “CAAX sequence”. In this sequence “C” is a cysteine, “A” represents an aliphatic amino acid and “X” can be variable. Transferable substrates have included a variety of probes that allow modified proteins and peptides to be subsequently targeted by various bioconjugation methods. These methods include copper-catalyzed click chemistry, oxime ligation, and strain-promoted reactions. Reported here is the synthesis and kinetic evaluation of a norbornene containing isoprenoid capable of site specific enzymatic transfer onto “CAAX” containing peptides. This norbornene modification will open the door to subsequent modification of proteins and peptides via a range of bioconjugation strategies including: photoclick chemistry with tetrazoles, inverse electron-demand Diels Alder reactions with functionalized tetrazines, and ring-opening metathesis polymerization. These strategies open new pathways for studying prenylateable proteins and the synthesis of peptide-polymer conjugates.

Synthesis and evaluation of a norbornene containing substrate for protein farnesyltransferase

253rd National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.