Evaluation of on-resin head-to-tail cyclization protocols of peptides using automated peptide synthesizers

To synthesize cyclic peptides, automated peptide synthesizers using solid phase supports have been the method of choice utilizing cyclization techniques such as lactam and disulfide bridges to impart cyclic structure. Head-to-tail cycles have proved difficult to perform on solid supports due to the C-terminus being bound to the solid support. More often than not, the cyclization reaction is performed in solution at high dilution levels. Some techniques have been developed that cleave and cyclize in a single reaction step however these reactions typically run overnight and result in a lower crude purity. Here we evaluated conditions to automate head-to-tail cyclization reactions while leaving the peptide on-resin to improve recovery and decrease synthesis times.

Literature number: P250