Methods for Protein and Peptide Cyclization

Abstract

Cyclic peptides have recently attracted a great deal of interest in drug discovery and pharmaceutical research. However, cyclic peptide isolation from intracellular space has proven to be challenging, limiting studies and screening methods for these small molecules. Recent attempts to isolate cyclic peptides from cell cytosol have utilized photocaged split inteins to allow for sequence purification prior to cyclization.1 Unfortunately, the proposed photocaged cyclization protocol does not yield efficient concentrations of cyclized product. Here, we propose several novel methods for peptide cyclization, demonstrating method viability by cyclizing GFP and other peptide sequences. Future research into cyclic peptides might benefit from these cyclization schemes, allowing for more in depth studies into cyclic peptide activity and more efficient drug design based on cyclic peptide scaffolds.