Amanda M. Heapy

Synthesis of a dicarba analogue of human β-defensin-1 using a combined ring closing metathesis--native chemical ligation strategy.

We herein describe the first synthesis of the native antimicrobial protein HBD-1 making use of an orthogonal thiol protection strategy and a novel dicarba analogue thereof. The robust hydrocarbon linkage was installed by replacement of one disulfide bond using on-resin ring closing metathesis. The unprecedented 59-membered C-terminal cysteine macrocyclic fragment thus formed then engages in native chemical ligation allowing convergent access to this unique synthetic protein analogue.

The synthesis of dehydrotryptophan and dehydrotryptophan-containing peptides

Dehydrotryptophan and its derivatives are non-proteinogenic amino acids commonly found in peptide-based natural products produced by microorganisms, marine organisms and plants. These non-proteinogenic amino acids are found in secondary metabolites and are formed by post translational modification processes. Although comprehensive reviews on the synthesis of dehydroamino acids are available, this perspective focuses solely on methods to synthesise the dehydrotryptophan-containing segment of naturally occurring peptides, amino acids and their derivatives.