Microwave-assisted Boc-solid phase peptide synthesis of cyclic cysteine-rich peptides

In this study we describe the first protocols for the synthesis of cystine‐rich peptides in the presence of microwave radiation with Boc‐solid phase peptide synthesis (SPPS). This method is exemplified for macrocyclic peptides known as cyclotides, which comprise ∼30 amino acids and incorporate a cystine knot arrangement of their three disulfide bonds. However, the method is broadly applicable for a wide range of peptides using Boc‐SPPS, especially for SPPS of large peptides via native chemical ligation. Microwave radiation produces peptides in high yield and with high purity, and we were able to reduce the time for the assembly of ∼30 mer peptide chains to an overnight reaction in the automated microwave‐assisted synthesis. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.