Synthesis of nonproteinogenic amino acids to probe lantibiotic biosynthesis.

Abstract

The synthesis of six nonproteinogenic amino acids appropriately protected for Fmoc-based solid-phase peptide synthesis is described. These amino acids are (2S,3R)-vinylthreonine, (2S)-(E)-2-amino-5-fluoro-pent-3-enoic acid (fluoroallylglycine), (S)-beta(2)-homoserine, (S) and (R)-beta(3)-homocysteine, and (2R,3R)-methylcysteine. Once incorporated into peptides, these compounds were envisioned to serve as alternative substrates for the lantibiotic synthases that dehydrate serine and threonine residues in their peptide substrates and catalyze the subsequent intramolecular Michael-type addition of cysteines to the dehydroamino acids.