Protein farnesyltransferase (PFTase) is an enzyme that incorporates farnesyl groups into proteins and peptides that end in a certain amino acid sequence. Previously, non-natural substrates have also been transferred by PFTase. These substrates contained azide and alkyne moieties that could subsequently undergo bioconjugation reactions via copper catalyzed click chemistry. However; because of copper’s cytotoxicity, these substrates were not compatible with many <i>in vivo</i> applications. Here progress toward the synthesis of an norbornene containing isoprenoid diphosphate is reported. Different protecting group strategies are highlighted in two possible synthetic routes for this target. One route includes an acetyl protection of an alcohol while the other includes THP protection. Once synthesis is complete this norbornene containing PFTase substrate will allow for subsequent bioconjugation of functionalized tetrazines without the use of copper catalysts. In end this will allow for the study of the prenylome inside living systems.

Progress towards the synthesis of a norbornene containing substrate for the enzyme protein farnesyltransferase

249th National Meeting (2015)

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