Translational synthesis of constrained cyclic peptides using genetic code reprogramming

Cyclic peptides are an emerging class of pharmaceutical. A key advantage of this chemical class is that they can be synthesised through biochemical processes, allowing the use of display screening techniques. This article describes one such process for cyclic peptide synthesis. This process employs genetic code reprogramming using an aminoacylating ribozyme to introduce a non-canonical amino acid. This includes methods for: (1) synthesis of the required ribozyme and an appropriate tRNA, (2) acylation of the tRNA with a non-canonical amino acid (3) the translation of a peptide incorporating the non-canonical amino acid, and (4) confirmation of the reaction by mass spectroscopy.